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Mendeliome v1.602 CRLS1 Zornitza Stark Phenotypes for gene: CRLS1 were changed from Mitochondrial disease MONDO:0044970 CRLS1-related to Combined oxidative phosphorylation deficiency 57, MIM# 620167
Mendeliome v1.601 CRLS1 Zornitza Stark edited their review of gene: CRLS1: Changed phenotypes: Combined oxidative phosphorylation deficiency 57, MIM# 620167
Mendeliome v1.601 TRPC5 Hazel Phillimore gene: TRPC5 was added
gene: TRPC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRPC5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TRPC5 were set to PMID: 36323681; 24817631; 23033978; 33504798; 28191890
Phenotypes for gene: TRPC5 were set to Intellectual disability; autistic spectrum disorder
Review for gene: TRPC5 was set to AMBER
Added comment: PMID: 36323681; Leitão E. et al. (2022) Nat Commun.13(1):6570:
Missense variant NM_012471.2:c.523C>T, p.(Arg175Cys in three brothers with intellectual disability (ID) and autistic spectrum disorder (ASD), inherited from an asymptomatic mother and absent in the maternal grandparents.
Whole cell patch clamp studies of HEK293 created by site-directed mutagenesis showed increased current of this calcium channel (constitutively opened).
(This variant is absent in gnomAD v2.1.1).

Also, the nonsense variant, c.965G> A, p.(Trp322*) was found in a high functioning ASD male (maternally inherited), NMD-predicted.

Other papers and TRPC5 variants that were cited to associate this gene with X-linked ID and/or ASD include:
PMID: 24817631; Mignon-Ravix, C. et al. (2014) Am. J.Med. Genet. A 164A: 1991–1997: A hemizygous 47-kb deletion in Xq23 including exon 1 of the TRPC5 gene. He had macrocephaly, delayed psychomotor development, speech delay, behavioural problems, and autistic features. Maternally inherited, and a family history compatible with X-linked inheritance (i.e., maternal great uncle was also affected, although not tested).

In addition, PMID: 36323681; Leitão E. et al. (2022) cites papers with the variants p.(Pro667Thr), p.(Arg71Gln) and p.(Trp225*).
NB. p.(Pro667Thr) is absent in gnomAD (v2.1.1), p.(Arg71Gln) is also absent (the alternative variant p.(Arg71Trp) is present once as heterozygous only). p.(Trp225*) is absent, and it should be noted that PTCs / LoF variants are very rare (pLI = 1).

However, looking further into the three references, the evidence is not as clear or as accurate as was stated.

The missense variant c.1999C>A, p.(Pro667Thr), was stated as de novo, but was actually maternally inherited but was still considered a candidate for severe intellectual disability (shown in the Appendix, Patient 93, with severe speech delay, autism spectrum disorder and Gilles de la Tourette). This patient also has a de novo MTF1 variant. Reference: PMID: 23033978; de Ligt, J. et al. (2012) N. Engl. J. Med. 367: 1921–1929).

Missense variant (de novo): c.212G>A, p.(Arg71Gln), was found as part of the Deciphering Developmental Disorders (DDD) study and is shown in individual 164 in Supplementary Table 2 of PMID: 33504798; Martin, HC. et al. (2021) Nat. Commun.12: 627. Also displayed in DECIPHER (DDD research variant) with several phenotype traits, but ID and ASD are not specifically mentioned.

Nonsense variant: c.674G>A. p.(Trp225*) was stated as de novo but was inherited (reference PMID: 28191890; Kosmicki, JA. et al. (2017) Nat. Genet. 49: 504–510. Supplement Table 7). This was a study of severe intellectual delay, developmental delay / autism. (NB. The de novo p.(Arg71Gln) variant from the DDD study is also listed (subject DDD 342 in Supplement 4 / Table 2).
Sources: Literature
Mendeliome v1.601 ZMYM3 Zornitza Stark Gene: zmym3 has been classified as Green List (High Evidence).
Mendeliome v1.601 BSN Krithika Murali changed review comment from: Ye et al 2022, Neurogenetics identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development.

In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected.

Association between biallelic variants and epilepsy stronger than for monoallelic.
Sources: Literature; to: Ye et al 2022, Neurogenetics - https://jmg.bmj.com/content/early/2022/12/12/jmg-2022-108865
Identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development.

In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected.

Association between biallelic variants and epilepsy stronger than for monoallelic.
Sources: Literature
Mendeliome v1.601 RIC1 Paul De Fazio reviewed gene: RIC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36493769; Phenotypes: Cleft lip/palate MONDO:0016044, RIC1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v1.601 UHRF1 Zornitza Stark Phenotypes for gene: UHRF1 were changed from Multi locus imprinting disturbance in offspring to Multi locus imprinting disturbance in offspring; chromosome instability
Mendeliome v1.600 UHRF1 Zornitza Stark Publications for gene: UHRF1 were set to 29574422; 28976982
Mendeliome v1.599 UHRF1 Zornitza Stark Mode of inheritance for gene: UHRF1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.598 SLC31A1 Zornitza Stark Publications for gene: SLC31A1 were set to PMID: 35913762
Mendeliome v1.597 SLC31A1 Zornitza Stark reviewed gene: SLC31A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36562171; Phenotypes: Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.597 BSN Zornitza Stark Added comment: Comment when marking as ready: We are aware of additional mono-allelic cases.
Mendeliome v1.597 BSN Zornitza Stark Gene: bsn has been classified as Green List (High Evidence).
Mendeliome v1.597 BSN Zornitza Stark Mode of inheritance for gene: BSN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.596 BSN Zornitza Stark Classified gene: BSN as Green List (high evidence)
Mendeliome v1.596 BSN Zornitza Stark Gene: bsn has been classified as Green List (High Evidence).
Mendeliome v1.595 UHRF1 Chern Lim changed review comment from: PMID: 29574422 Begemann et al. 2018
- Het missense in mother and proband, family recruited due to detection of multilocus imprinting disturbance (MLID) in offspring. Proband is one of discordant monozygotic twin. SRS: NH-CSS 5/6; also kidney failure in infancy, bilateral renal dysplasia. Variant present in both twins, no functional studies done on the missense.; to: PMID: 29574422 Begemann et al. 2018
- Het missense in mother and proband, family recruited due to detection of multilocus imprinting disturbance (MLID) in offspring. Proband is one of discordant monozygotic twin. SRS: NH-CSS 5/6; also kidney failure in infancy, bilateral renal dysplasia. Variant present in both twins, no functional studies done on the missense. Her cotwin was clinically and epigenetically normal
Mendeliome v1.595 ARHGAP35 Zornitza Stark Phenotypes for gene: ARHGAP35 were changed from neurodevelopmental disorder, ARHGAP35-related MONDO#0700092 to neurodevelopmental disorder, ARHGAP35-related MONDO#0700092; Developmental defect of the eye (MONDO:0020145), ARHGAP35-related
Mendeliome v1.594 ARHGAP35 Zornitza Stark Publications for gene: ARHGAP35 were set to 33057194
Mendeliome v1.593 UHRF1 Chern Lim edited their review of gene: UHRF1: Changed publications: 36458887, 29574422; Changed phenotypes: chromosome instability, Multi locus imprinting disturbance in offspring; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.593 ARHGEF38 Zornitza Stark Gene: arhgef38 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.593 UHRF1 Chern Lim edited their review of gene: UHRF1: Added comment: PMID: 36458887 Unoki et al. 2022
- One patient with compound het missense and nonsense variants, both parents are carriers (hets).
- The patient has chromosome instability with hypomethylation of the pericentromeric satellite-2 repeats and facial anomalies as typical symptoms of the ICF syndrome, but did not exhibit immunodeficiency, and developed an adrenocortical adenoma; characteristics that were atypical.
- Genome-wide methylation analysis revealed the patient had a centromeric/pericentromeric hypomethylation, which is the main ICF signature, but also had a distinctive hypomethylation pattern compared to patients with the other ICF syndrome subtypes.
- Structural and biochemical analyses revealed that the R296W variant disrupted the protein conformation and strengthened the binding affinity of UHRF1 with its partner LIG1, and reduced ubiquitylation activity of UHRF1 towards its ubiquitylation substrates, histone H3 and PAF15.; Changed publications: 36458887; Changed phenotypes: chromosome instability; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.593 ARHGEF38 Zornitza Stark Mode of inheritance for gene: ARHGEF38 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.592 ARHGEF38 Zornitza Stark Classified gene: ARHGEF38 as Amber List (moderate evidence)
Mendeliome v1.592 ARHGEF38 Zornitza Stark Gene: arhgef38 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.591 UHRF1 Chern Lim reviewed gene: UHRF1: Rating: RED; Mode of pathogenicity: None; Publications: 29574422; Phenotypes: Multi locus imprinting disturbance in offspring; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.591 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Mendeliome v1.591 EIF4A2 Zornitza Stark Classified gene: EIF4A2 as Green List (high evidence)
Mendeliome v1.591 EIF4A2 Zornitza Stark Gene: eif4a2 has been classified as Green List (High Evidence).
Mendeliome v1.590 ARHGAP35 Dean Phelan reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36450800; Phenotypes: Developmental defect of the eye (MONDO:0020145), ARHGAP35-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.590 SLC31A1 Alison Yeung Classified gene: SLC31A1 as Amber List (moderate evidence)
Mendeliome v1.590 SLC31A1 Alison Yeung Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.589 ARHGEF38 Paul De Fazio gene: ARHGEF38 was added
gene: ARHGEF38 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGEF38 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGEF38 were set to 36493769
Phenotypes for gene: ARHGEF38 were set to Cleft lip/palate MONDO:0016044, ARHGEF38-related
Review for gene: ARHGEF38 was set to AMBER
gene: ARHGEF38 was marked as current diagnostic
Added comment: PMID:36493769 identified an intragenic deletion by high-res microarray of the same exon (exon 3) in 4 individuals with non-syndromic cleft lip/palate. Deletion of exon 3 is present in 6 individuals in gnomAD. Inheritance information was not available.

Knockdown and knockout of the gene in Xenopus and Zebrafish resulted in craniofacial malformations in a large proportion (but not 100%) of embryos.
Sources: Literature
Mendeliome v1.589 COBLL1 Zornitza Stark Gene: cobll1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.589 COBLL1 Zornitza Stark Classified gene: COBLL1 as Amber List (moderate evidence)
Mendeliome v1.589 COBLL1 Zornitza Stark Gene: cobll1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.588 COBLL1 Paul De Fazio edited their review of gene: COBLL1: Changed rating: AMBER
Mendeliome v1.588 COBLL1 Paul De Fazio gene: COBLL1 was added
gene: COBLL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COBLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COBLL1 were set to 36493769
Phenotypes for gene: COBLL1 were set to Cleft lip/palate MONDO:0016044, COBLL1-related
gene: COBLL1 was marked as current diagnostic
Added comment: PMID:36493769 identified the same multi-exon intragenic deletion by high-res microarray in 3 individuals with non-syndromic cleft lip/palate. The deletion is absent from gnomAD. Inheritance information was only available for 1 individual, in whom it was inherited from an unaffected father. Note that the gene is not quite LOF constrained in gnomAD.

Knockdown and knockout of the gene in Xenopus and Zebrafish resulted in craniofacial malformations in a large proportion (but not 100%) of embryos.
Sources: Literature
Mendeliome v1.588 BSN Krithika Murali gene: BSN was added
gene: BSN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BSN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BSN were set to Epilepsy MONDO:0005027
Review for gene: BSN was set to GREEN
Added comment: Ye et al 2022, Neurogenetics identified 4 unrelated individuals with epilepsy and compound heterozygous BSN variants via trio WES (combination of null and missense). Homozygous knockout mouse models showed abnormal CNS transmission and seizure activity. None of the identified variants were present in population databases as homozygotes. One individual had ID and microcephaly but all other individuals with biallelic variants had normal development.

In addition, heterozygous variants were identified in unrelated affected individuals - 2 apparently co-segregating missense variants and 2 de novo null variants. These variants were either absent in population databases or rare. The authors note that affected individuals with heterozygous variants had milder disease - either requiring no therapy or monotherapy only. Heterozygous knockout mice had no phenotype and there were not enough affected individuals in the families to truly determine co-segregation. In addition, carrier parents of individuals with biallelic variants did not appear to be affected.

Association between biallelic variants and epilepsy stronger than for monoallelic.
Sources: Literature
Mendeliome v1.588 EIF4A2 Dean Phelan gene: EIF4A2 was added
gene: EIF4A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EIF4A2 were set to PMID: 36528028
Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related
Mode of pathogenicity for gene: EIF4A2 was set to Other
Review for gene: EIF4A2 was set to GREEN
Added comment: PMID: 36528028
- EIF4A2 variants were observed in 15 individuals from 14 families. Affected individuals had a range of symptoms including global developmental delay (9/15), ID (7/15), epilepsy (11/15) and structural brain alterations (10/15). Monoallelic and biallelic variants were reported and functional studies showed both LOF and GOF disease mechanisms.
Sources: Literature
Mendeliome v1.588 OXGR1 Sarah Pantaleo edited their review of gene: OXGR1: Changed phenotypes: Nephrolithiasis/nephrocalcinosis, MONDO:0008171, OXGR1-related, MONDO:0001567, OXGR1-related
Mendeliome v1.588 PHLDB1 Seb Lunke Gene: phldb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.588 PHLDB1 Seb Lunke Classified gene: PHLDB1 as Amber List (moderate evidence)
Mendeliome v1.588 PHLDB1 Seb Lunke Gene: phldb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.587 PHLDB1 Seb Lunke gene: PHLDB1 was added
gene: PHLDB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PHLDB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHLDB1 were set to 36543534
Phenotypes for gene: PHLDB1 were set to osteogenesis imperfecta, MONDO:0019019
Review for gene: PHLDB1 was set to AMBER
Added comment: 5 children from two consanguineous families with recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment.

Two independent nonsense variants were identified in the families, NM_001144758.3:c.2392dup (p.Leu798Profs*4) and NM_001144758.3:c.2690_2693del (p.Leu897Glnfs*24). RT-PCR and western blot analysis confirmed loss of transcript and protein product, respectively, but no further functional data provided.
Sources: Literature
Mendeliome v1.586 OXGR1 Zornitza Stark Gene: oxgr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.586 OXGR1 Zornitza Stark Classified gene: OXGR1 as Amber List (moderate evidence)
Mendeliome v1.586 OXGR1 Zornitza Stark Gene: oxgr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.585 CDK16 Alison Yeung Phenotypes for gene: CDK16 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO#0700092) CDK16-related
Mendeliome v1.584 CDK16 Alison Yeung Publications for gene: CDK16 were set to 25644381
Mendeliome v1.583 OXGR1 Sarah Pantaleo gene: OXGR1 was added
gene: OXGR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OXGR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OXGR1 were set to PMID:35671463
Phenotypes for gene: OXGR1 were set to Nephrolithiasis/nephrocalcinosis MONDO:0008171, OXGR1-related
Penetrance for gene: OXGR1 were set to unknown
Review for gene: OXGR1 was set to AMBER
Added comment: Candidate disease gene for human calcium oxalate nephrolithiasis.

Performed exome sequencing and directed sequencing of the OXGR1 locus in a worldwide nephrolithiasis/nephrocalcinosis (NL/NC) cohort, and putatively deleterious rare OXGR1 variants were functionally characterised.

A heterozygous OXGR1 missense variant (c.371T>G; p.Leu124Arg) co-segregated with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multi-generational family with five affected individuals.

Interrogation of the OXGR1 locus in 1,107 additional NL/NC families identified five additional deleterious dominant variants in five families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in NL/NC subjects relative to ExAC controls. Four missense variants and one frameshift variant.

Four of five NL/NC-associated missense variants revealed impaired AKG-dependent calcium ion uptake, demonstrating loss of function.

Rare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease. Six potentially deleterious variants were identified in six of 1,108 NL/NC families (0.54%).

Limitations: only probands were able to be recruited for four of six families. In the future, it will be important to determine whether any of the affected family members share the identified OXGR1 variant. They also observe OXGR1 variants in 0.16% of ExAC subjects (selected on the basis of the absence of paediatric disease).
Sources: Literature
Mendeliome v1.583 CDK16 Alison Yeung reviewed gene: CDK16: Rating: GREEN; Mode of pathogenicity: None; Publications: 36323681, 31981491, 25644381; Phenotypes: Neurodevelopmental disorder (MONDO#0700092) CDK16-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.583 CDK16 Alison Yeung Classified gene: CDK16 as Green List (high evidence)
Mendeliome v1.583 CDK16 Alison Yeung Gene: cdk16 has been classified as Green List (High Evidence).
Mendeliome v1.582 CCIN Seb Lunke Gene: ccin has been classified as Green List (High Evidence).
Mendeliome v1.582 CCIN Seb Lunke Phenotypes for gene: CCIN were changed from Teratozoospermia to male infertility with teratozoospermia due to single gene mutation, MONDO:0018394
Mendeliome v1.581 CCIN Seb Lunke Classified gene: CCIN as Green List (high evidence)
Mendeliome v1.581 CCIN Seb Lunke Gene: ccin has been classified as Green List (High Evidence).
Mendeliome v1.580 CCIN Chern Lim gene: CCIN was added
gene: CCIN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCIN were set to 36546111; 36527329
Phenotypes for gene: CCIN were set to Teratozoospermia
Review for gene: CCIN was set to GREEN
gene: CCIN was marked as current diagnostic
Added comment: Two papers with three unrelated patients with teratozoospermia:

PMID: 36546111
- Two families reported: One with homozygous missense (fam is consanguineous) and another with compound heterozygous missense + nonsense variants, patients suffering from teratozoospermia.
- Homozygous CcinH42L/H42L and compound heterozygous CcinR432W/C447* knock-in mice generated. Spermatozoa from homozygous male mice exhibited abnormalities of sperm head shape revealed by Diff-Quick staining. When mated with WT mice, both homozygous CcinH42L/H42L and compound heterozygous CcinR432W/C447* male mice were infertile, whereas the mutant female mice could generate offspring and displayed no defects in fertility.

PMID: 36527329
- One consanguineous family reported: homozygous missense, with asthenoteratozoospermia.
- Transfected HEK cells showed reduced CCIN protein level.
Sources: Literature
Mendeliome v1.580 TRA2B Seb Lunke Marked gene: TRA2B as ready
Mendeliome v1.580 TRA2B Seb Lunke Gene: tra2b has been classified as Green List (High Evidence).
Mendeliome v1.580 TRA2B Seb Lunke Phenotypes for gene: TRA2B were changed from Neurodevelopmental disorder, TRA2B-related (MONDO#0700092) to Neurodevelopmental disorder, TRA2B-related, MONDO# 0700092
Mendeliome v1.579 TRA2B Seb Lunke Classified gene: TRA2B as Green List (high evidence)
Mendeliome v1.579 TRA2B Seb Lunke Gene: tra2b has been classified as Green List (High Evidence).
Mendeliome v1.578 ZMYM3 Zornitza Stark Mode of inheritance for gene: ZMYM3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.577 ZMYM3 Zornitza Stark Phenotypes for gene: ZMYM3 were changed from Neurodevelopmental disorders (NDDs) to Neurodevelopmental disorder, MONDO:0700092, ZMYM3-related
Mendeliome v1.576 TRA2B Elena Savva gene: TRA2B was added
gene: TRA2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRA2B were set to PMID: 36549593
Phenotypes for gene: TRA2B were set to Neurodevelopmental disorder, TRA2B-related (MONDO#0700092)
Review for gene: TRA2B was set to GREEN
Added comment: PMID: 36549593
- 12 individuals with ID and dev delay. Additional features include infantile spams 6/12, hypotonia 12/12, dilated brain ventricles 6/12, microcephaly 5/12
- All variants result in the loss of 1/2 transcripts (start-losses or PTCs upstream of a second translation start position). Shorter transcript expression is increased, longer transcript expression is decreased.
- Apparently het mice K/O are normal, but complete K/O cannot develop embryonically.
- DN mechanism suggested
Sources: Literature
Mendeliome v1.575 ZMYM3 Zornitza Stark Classified gene: ZMYM3 as Green List (high evidence)
Mendeliome v1.575 ZMYM3 Zornitza Stark Gene: zmym3 has been classified as Green List (High Evidence).
Mendeliome v1.574 TUFT1 Zornitza Stark Marked gene: TUFT1 as ready
Mendeliome v1.574 TUFT1 Zornitza Stark Gene: tuft1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.574 TUFT1 Zornitza Stark Classified gene: TUFT1 as Amber List (moderate evidence)
Mendeliome v1.574 TUFT1 Zornitza Stark Gene: tuft1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.573 TUFT1 Zornitza Stark gene: TUFT1 was added
gene: TUFT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUFT1 were set to https://doi.org/10.1093/bjd/ljac026
Phenotypes for gene: TUFT1 were set to Ectodermal dysplasia, MONDO:0019287, TUFT1-related
Review for gene: TUFT1 was set to AMBER
Added comment: 9 individuals from three families reported with woolly hair and skin fragility. One of the variants, c.60+1G>A was present in two of the families, founder effect demonstrated by haplotype analysis. Another loss of function variant present in the third family. Some functional data but mostly expression studies.
Sources: Literature
Mendeliome v1.572 ZMYM3 Belinda Chong gene: ZMYM3 was added
gene: ZMYM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZMYM3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZMYM3 were set to 36586412; 24721225
Phenotypes for gene: ZMYM3 were set to Neurodevelopmental disorders (NDDs)
Review for gene: ZMYM3 was set to GREEN
Added comment: PMID: 36586412
Using the MatchMaker Exchange - Described 27 individuals with rare, variation in the ZMYM3. Most individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) with de novo variants.
Overlapping features included developmental delay, intellectual disability, behavioural abnormalities, and a specific facial gestalt in a subset of males.
Variants in almost all individuals are missense, including six that recurrently affect two residues. Four unrelated probands were identified with inherited variation affecting Arg441 (R441W), a site at which variation has been previously seen in NDD-affected siblings (24721225), and two individuals have de novo variation resulting in p.Arg1294Cys (c.3880C>T).
ChIP-seq experiments on one variant, p.Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect.
Sources: Literature
Mendeliome v1.572 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome to Kabuki syndrome 1, MIM# 147920; Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH), MIM#620186
Mendeliome v1.571 KMT2D Zornitza Stark edited their review of gene: KMT2D: Changed phenotypes: Kabuki syndrome 1, MIM# 147920, Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH), MIM#620186
Mendeliome v1.571 BUB1 Zornitza Stark Phenotypes for gene: BUB1 were changed from Neurodevelopmental disorder, BUB1-related MONDO:0700092 to Primary microcephaly-30 (MCPH30), MIM#620183
Mendeliome v1.570 BUB1 Zornitza Stark edited their review of gene: BUB1: Changed phenotypes: primary microcephaly-30 (MCPH30), MIM#620183
Mendeliome v1.570 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from Epilepsy, progressive myoclonic 6 , MIM#614018 to Epilepsy, progressive myoclonic 6 , MIM#614018; Muscular dystrophy, congenital, with or without seizures, MIM# 620166
Mendeliome v1.569 GOSR2 Zornitza Stark edited their review of gene: GOSR2: Added comment: PMIDs 29855340; 33639315: at least three families reported with a muscular dystrophy presentation as well as seizures.; Changed publications: 21549339, 24458321, 30363482, 29855340, 33639315; Changed phenotypes: Epilepsy, progressive myoclonic 6 , MIM#614018, Muscular dystrophy, congenital, with or without seizures, MIM# 620166
Mendeliome v1.569 TNNC2 Zornitza Stark Phenotypes for gene: TNNC2 were changed from Congenital myopathy, MONDO:0019952, TNNC2-related to Myopathy, congenital, with neonatal respiratory insufficiency, MIM# 620161
Mendeliome v1.568 TNNC2 Zornitza Stark edited their review of gene: TNNC2: Changed phenotypes: Myopathy, congenital, with neonatal respiratory insufficiency, MIM# 620161
Mendeliome v1.568 C3orf52 Zornitza Stark Phenotypes for gene: C3orf52 were changed from Localized hypotrichosis to Hypotrichosis-15, MIM#620177
Mendeliome v1.567 C3orf52 Zornitza Stark edited their review of gene: C3orf52: Changed phenotypes: Hypotrichosis-15, MIM#620177
Mendeliome v1.567 TSPEAR Zornitza Stark Phenotypes for gene: TSPEAR were changed from Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180 to Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis, MIM#618180; Selective tooth agenesis-10 (STHAG10), MIM#620173
Mendeliome v1.566 TSPEAR Zornitza Stark Publications for gene: TSPEAR were set to 27736875; 30046887
Mendeliome v1.565 TSPEAR Zornitza Stark edited their review of gene: TSPEAR: Added comment: More than 5 individuals reported with selective tooth agenesis.; Changed rating: GREEN; Changed publications: 30046887, 32112661, 34042254; Changed phenotypes: Selective tooth agenesis-10 (STHAG10), MIM#620173; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.565 CDK5 Zornitza Stark Publications for gene: CDK5 were set to 25560765
Mendeliome v1.564 CDK5 Zornitza Stark Classified gene: CDK5 as Amber List (moderate evidence)
Mendeliome v1.564 CDK5 Zornitza Stark Gene: cdk5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.563 CDK5 Zornitza Stark edited their review of gene: CDK5: Added comment: Upgraded to Amber following GenCC discrepancy resolution: single family with four affected individuals but extensive supportive experimental evidence including mouse models.; Changed rating: AMBER; Changed publications: 25560765, 32273484, 32097629, 28854363, 7490100
Mendeliome v1.563 SLC26A6 Arina Puzriakova gene: SLC26A6 was added
gene: SLC26A6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC26A6 were set to 35115415; 21170874; 32660969
Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis
Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969)

SLC26A6 is currently not associated with any human phenotype in OMIM or G2P.
Sources: Literature
Mendeliome v1.563 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from Microcephaly 18, primary, autosomal dominant, MIM#617520 to Microcephaly 18, primary, autosomal dominant, MIM#617520; Neurodevelopmental disorder with macrocephaly
Mendeliome v1.562 PTPN4 Zornitza Stark Phenotypes for gene: PTPN4 were changed from Intellectual disability; developmental delay to Neurodevelopmental disorder, MONDO:0700092, PTPN4-related
Mendeliome v1.561 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from alternating hemiplegia, MONDO:0016210, CLDN5-related to Syndromic disorder, MONDO:0002254, CLDN5-related
Mendeliome v1.560 CLDN5 Zornitza Stark Publications for gene: CLDN5 were set to 35714222
Mendeliome v1.559 CLDN5 Zornitza Stark Mode of pathogenicity for gene: CLDN5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.558 CLDN5 Zornitza Stark Classified gene: CLDN5 as Green List (high evidence)
Mendeliome v1.558 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Green List (High Evidence).
Mendeliome v1.557 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from Luscan-Lumish syndrome, MIM#616831; Luscan-Lumish syndrome, MIM#616831; Rabin-Pappas syndrome,MIM# 620155; Intellectual developmental disorder, autosomal dominant 70, MIM# 620157 to Luscan-Lumish syndrome, MIM#616831; Rabin-Pappas syndrome,MIM# 620155; Intellectual developmental disorder, autosomal dominant 70, MIM# 620157
Mendeliome v1.556 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from Luscan-Lumish syndrome, MIM#616831 to Luscan-Lumish syndrome, MIM#616831; Luscan-Lumish syndrome, MIM#616831; Rabin-Pappas syndrome,MIM# 620155; Intellectual developmental disorder, autosomal dominant 70, MIM# 620157
Mendeliome v1.555 SETD2 Zornitza Stark Publications for gene: SETD2 were set to 29681085
Mendeliome v1.554 SETD2 Zornitza Stark edited their review of gene: SETD2: Added comment: PMID 32710489: 12 unrelated patients, ranging from 1 month to 12 years of age, with a multisystemic neurodevelopmental disorder associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740W).

Key clinical features: severely impaired global development apparent from infancy, feeding difficulties with failure to thrive, small head circumference, and dysmorphic facial features. Affected individuals have impaired intellectual development and hypotonia; they do not achieve walking or meaningful speech. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and possibly endocrine.

Further 3 unrelated patients identified with mild to moderately impaired intellectual development associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740Q).

These are distinct clinically from Luscan-Lumish syndrome, which is characterised by overgrowth.; Changed publications: 29681085, 32710489; Changed phenotypes: Luscan-Lumish syndrome, MIM#616831, Rabin-Pappas syndrome,MIM# 620155, Intellectual developmental disorder, autosomal dominant 70, MIM# 620157
Mendeliome v1.554 RPS15 Zornitza Stark Gene: rps15 has been classified as Red List (Low Evidence).
Mendeliome v1.554 RPS15 Zornitza Stark Phenotypes for gene: RPS15 were changed from Diamond-Blackfan anaemia to Diamond-Blackfan anaemia, MONDO:0015253, RPS15-related
Mendeliome v1.553 RPS15 Zornitza Stark gene: RPS15 was added
gene: RPS15 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RPS15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS15 were set to 19061985
Phenotypes for gene: RPS15 were set to Diamond-Blackfan anaemia
Review for gene: RPS15 was set to RED
Added comment: Single individual reported in 2008, no reports since.
Sources: Expert Review
Mendeliome v1.552 CLDN5 Suliman Khan reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 36477332; Phenotypes: seizures, developmental delay, microcephaly, brain calcifications; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.552 AMT Xinyu Zhang reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 35646099, 25231368, 27362913; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.552 KIF26A Zornitza Stark Phenotypes for gene: KIF26A were changed from Cerebral malformation MONDO:0016054, KIF26-related to Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Mendeliome v1.551 KIF26A Zornitza Stark edited their review of gene: KIF26A: Changed phenotypes: Cortical dysplasia, complex, with other brain malformations 11, MIM# 620156
Mendeliome v1.551 ZFP36L1 Zornitza Stark Phenotypes for gene: ZFP36L1 were changed from to Oocyte maturation defect 13, MIM# 620154
Mendeliome v1.550 ZFP36L1 Zornitza Stark Publications for gene: ZFP36L1 were set to
Mendeliome v1.549 ZFP36L1 Zornitza Stark Mode of inheritance for gene: ZFP36L1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.548 ZFP36L1 Zornitza Stark reviewed gene: ZFP36L1: Rating: RED; Mode of pathogenicity: None; Publications: 34611029, 22367205; Phenotypes: Oocyte maturation defect 13, MIM# 620154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.548 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from Dyssegmental dysplasia, Silverman-Handmaker type; Schwartz-Jampel syndrome, type 1 to Schwartz-Jampel syndrome, type 1, MIM# 255800; MONDO:0009717; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; MONDO:0009140
Mendeliome v1.547 IL2RB Zornitza Stark Tag immunological was removed from gene: IL2RB.
Mendeliome v1.547 IL2RB Zornitza Stark Tag treatable tag was added to gene: IL2RB.
Tag immunological tag was added to gene: IL2RB.
Mendeliome v1.547 IL2RB Zornitza Stark changed review comment from: Five families reported.
Sources: Expert list; to: Five families reported.

Affected individuals present in infancy with features of both abnormal activation of certain immune signaling pathways, resulting in lymphoid proliferation, dermatitis, enteropathy, and hypergammaglobulinemia, as well as features of immunodeficiency, such as recurrent infections and increased susceptibility to viral infections, especially CMV. Laboratory studies show increased NK cells that show impaired differentiation, as well as abnormal T cell populations or responses. Some patients may die in childhood; hematopoietic bone marrow transplantation is curative.

Sources: Expert list
Mendeliome v1.547 CACNA2D1 Zornitza Stark Phenotypes for gene: CACNA2D1 were changed from Developmental and epileptic encephalopathy disorder MONDO:0100062 CACNA2D1-related to Developmental and epileptic encephalopathy 110, MIM# 620149
Mendeliome v1.546 FZR1 Zornitza Stark Phenotypes for gene: FZR1 were changed from Developmental and epileptic encephalopathy, FZR1-related, MONDO:0100062 to Developmental and epileptic encephalopathy 109, MIM# 620145
Mendeliome v1.545 FZR1 Zornitza Stark reviewed gene: FZR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 109, MIM# 620145; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.545 SLC9A3R1 Zornitza Stark Tag refuted tag was added to gene: SLC9A3R1.
Mendeliome v1.545 IDS Zornitza Stark Mode of inheritance for gene: IDS was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.544 IDS Zornitza Stark edited their review of gene: IDS: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.544 RPS6KB1 Zornitza Stark Gene: rps6kb1 has been classified as Green List (High Evidence).
Mendeliome v1.544 RPS6KB1 Zornitza Stark Phenotypes for gene: RPS6KB1 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045, RPS6KB1-related
Mendeliome v1.543 RPS6KB1 Zornitza Stark Classified gene: RPS6KB1 as Green List (high evidence)
Mendeliome v1.543 RPS6KB1 Zornitza Stark Gene: rps6kb1 has been classified as Green List (High Evidence).
Mendeliome v1.542 TNNC2 Zornitza Stark Marked gene: TNNC2 as ready
Mendeliome v1.542 TNNC2 Zornitza Stark Gene: tnnc2 has been classified as Green List (High Evidence).
Mendeliome v1.542 TNNC2 Zornitza Stark Classified gene: TNNC2 as Green List (high evidence)
Mendeliome v1.542 TNNC2 Zornitza Stark Gene: tnnc2 has been classified as Green List (High Evidence).
Mendeliome v1.541 TNNC2 Zornitza Stark gene: TNNC2 was added
gene: TNNC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNC2 were set to 33755597
Phenotypes for gene: TNNC2 were set to Congenital myopathy, MONDO:0019952, TNNC2-related
Review for gene: TNNC2 was set to GREEN
Added comment: Two families reported: Family 1: 4 individuals, three generations; missense variant p.(Asp34Tyr) Family 2: de novo variant, missense p.(Met79Ile)

Physiological studies in myofibers isolated from patients’ biopsies revealed a markedly reduced force response of the sarcomeres to [Ca2+]. This pathomechanism was further confirmed in experiments in which contractile dysfunction was evoked by replacing TnC in myofibers from healthy control subjects with recombinant, mutant TnC. Conversely, the contractile dysfunction of myofibers from patients was repaired by replacing endogenous, mutant TnC with recombinant, wild-type TnC.

Borderline Green: sufficient segregation in Fam 1 plus de novo status in Fam 2, plus functional data.
Sources: Literature
Mendeliome v1.540 JAK3 Zornitza Stark Tag treatable tag was added to gene: JAK3.
Mendeliome v1.540 CHUK Zornitza Stark Phenotypes for gene: CHUK were changed from Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome to Combined immunodeficiency, MONDO:0015131, CHUK-related; Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339; Cocoon syndrome, MIM# 613630; AEC-like syndrome
Mendeliome v1.539 CHUK Zornitza Stark Publications for gene: CHUK were set to 25691407; 20961246; 10195895; 10195896; 29523099; 28513979
Mendeliome v1.538 CHUK Zornitza Stark edited their review of gene: CHUK: Changed phenotypes: Combined immunodeficiency, MONDO:0015131, CHUK-related, Popliteal pterygium syndrome, Bartsocas-Papas type 2, MIM# 619339, Cocoon syndrome, MIM# 613630, AEC-like syndrome
Mendeliome v1.538 CHUK Zornitza Stark edited their review of gene: CHUK: Added comment: PMID 34533979: single individual reported with homozygous missense variant in this gene and recurrent infections, skeletal abnormalities, absent secondary lymphoid structures, reduced B cell numbers, hypogammaglobulinemia, and lymphocytic infiltration of intestine. Supportive functional data.; Changed publications: 25691407, 20961246, 10195895, 10195896, 29523099, 28513979, 34533979
Mendeliome v1.538 IRF7 Zornitza Stark Publications for gene: IRF7 were set to 25814066; 15800576
Mendeliome v1.537 IRF7 Zornitza Stark Classified gene: IRF7 as Green List (high evidence)
Mendeliome v1.537 IRF7 Zornitza Stark Gene: irf7 has been classified as Green List (High Evidence).
Mendeliome v1.536 IRF7 Zornitza Stark Classified gene: IRF7 as Green List (high evidence)
Mendeliome v1.536 IRF7 Zornitza Stark Gene: irf7 has been classified as Green List (High Evidence).
Mendeliome v1.535 IRF7 Zornitza Stark edited their review of gene: IRF7: Changed rating: GREEN
Mendeliome v1.535 IRF7 Zornitza Stark edited their review of gene: IRF7: Added comment: Additional individuals reported PMIDs 35986347, 35670811: total of 7; Changed publications: 25814066, 15800576, 35986347, 35670811
Mendeliome v1.535 LIG1 Zornitza Stark Phenotypes for gene: LIG1 were changed from Combined immunodeficiency; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis to Immunodeficiency 96, MIM# 619774; Lymphopaenia; Hypogammaglobulinaemia; Recurrent bacterial and viral infections; Growth retardation; Sun sensitivity, radiation sensitivity; Macrocytosis
Mendeliome v1.534 NLGN4X Zornitza Stark Added comment: Comment when marking as ready: Definitive assessment by ClinGen noted, as well as 'limited' assessments by G2P and Genomics England. Many of the variants are multi-gene deletions; phenotypes are not well delineated, with several individuals not having ID.
Mendeliome v1.534 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Amber List (Moderate Evidence).
Mendeliome v1.534 NLGN4X Zornitza Stark Publications for gene: NLGN4X were set to 12669065; 18231125; 10071191; 29428674
Mendeliome v1.533 NLGN4X Zornitza Stark Classified gene: NLGN4X as Amber List (moderate evidence)
Mendeliome v1.533 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Amber List (Moderate Evidence).
Mendeliome v1.532 NLGN4X Krithika Murali reviewed gene: NLGN4X: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:26350204, PMID:14963808, PMID:12669065, PMID:23352163, PMID:28263302, PMID:16648374; Phenotypes: Intellectual developmental disorder, X-linked - MIM#300495; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v1.532 TIMMDC1 Zornitza Stark Classified gene: TIMMDC1 as Green List (high evidence)
Mendeliome v1.532 TIMMDC1 Zornitza Stark Gene: timmdc1 has been classified as Green List (High Evidence).
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.531 MPC2 Zornitza Stark Classified gene: MPC2 as Amber List (moderate evidence)
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.530 MPC2 Zornitza Stark gene: MPC2 was added
gene: MPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPC2 were set to 36417180
Phenotypes for gene: MPC2 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: MPC2 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.529 Zornitza Stark removed gene:NPC1 from the panel
Mendeliome v1.528 ARF3 Zornitza Stark Publications for gene: ARF3 were set to 34346499
Mendeliome v1.527 ARF3 Zornitza Stark Classified gene: ARF3 as Green List (high evidence)
Mendeliome v1.527 ARF3 Zornitza Stark Gene: arf3 has been classified as Green List (High Evidence).
Mendeliome v1.526 TIMMDC1 Paul De Fazio reviewed gene: TIMMDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36349561, 33278652; Phenotypes: Mitochondrial complex I deficiency, nuclear type 31 MIM#618251; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.526 LEMD2 Seb Lunke Phenotypes for gene: LEMD2 were changed from Marbach-Rustad progeroid syndrome, OMIM# 619322; progeroid disorder to Marbach-Rustad progeroid syndrome, OMIM# 619322; arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587; Cataract 46, juvenile-onset, OMIM# 212500
Mendeliome v1.525 LEMD2 Seb Lunke Publications for gene: LEMD2 were set to PMID: 30905398
Mendeliome v1.524 LEMD2 Seb Lunke Mode of inheritance for gene: LEMD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.523 LEMD2 Seb Lunke reviewed gene: LEMD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31061923, 26788539, 30905398, 36377660; Phenotypes: Marbach-Rustad progeroid syndrome, OMIM# 619322, arrhythmogenic right ventricular cardiomyopathy, MONDO:0016587, Cataract 46, juvenile-onset, OMIM# 212500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.523 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.523 NUP54 Zornitza Stark Phenotypes for gene: NUP54 were changed from Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mendeliome v1.522 NUP54 Zornitza Stark Mode of pathogenicity for gene: NUP54 was changed from None to None
Mendeliome v1.521 UQCRH Zornitza Stark Classified gene: UQCRH as Amber List (moderate evidence)
Mendeliome v1.521 UQCRH Zornitza Stark Gene: uqcrh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.520 FEM1C Zornitza Stark Gene: fem1c has been classified as Green List (High Evidence).
Mendeliome v1.520 FEM1C Zornitza Stark Classified gene: FEM1C as Green List (high evidence)
Mendeliome v1.520 FEM1C Zornitza Stark Gene: fem1c has been classified as Green List (High Evidence).
Mendeliome v1.519 DCLRE1B Zornitza Stark Phenotypes for gene: DCLRE1B were changed from Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome to Dyskeratosis congenita, autosomal recessive 8, MIM# 620133
Mendeliome v1.518 DCLRE1B Zornitza Stark Publications for gene: DCLRE1B were set to 20479256; 21647296
Mendeliome v1.517 DCLRE1B Zornitza Stark Mode of inheritance for gene: DCLRE1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.516 DCLRE1B Zornitza Stark Classified gene: DCLRE1B as Green List (high evidence)
Mendeliome v1.516 DCLRE1B Zornitza Stark Gene: dclre1b has been classified as Green List (High Evidence).
Mendeliome v1.515 DCLRE1B Zornitza Stark edited their review of gene: DCLRE1B: Added comment: Three additional families reported.; Changed rating: GREEN; Changed publications: 20479256, 21647296, 35007328
Mendeliome v1.515 NUP54 Zornitza Stark Mode of pathogenicity for gene: NUP54 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.514 NUP54 Zornitza Stark Classified gene: NUP54 as Amber List (moderate evidence)
Mendeliome v1.514 NUP54 Zornitza Stark Gene: nup54 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.513 NUP54 Hazel Phillimore gene: NUP54 was added
gene: NUP54 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP54 were set to PMID: 36333996
Phenotypes for gene: NUP54 were set to Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia
Mode of pathogenicity for gene: NUP54 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: NUP54 was set to AMBER
Added comment: From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544.

Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser).

Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu).

Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe)

The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum.

Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina.

Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.
Sources: Literature
Mendeliome v1.513 GABRA3 Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence).
Mendeliome v1.513 GABRA3 Zornitza Stark Phenotypes for gene: GABRA3 were changed from Epilepsy, intellectual disability, dysmorphic features, to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, MIM# 301091
Mendeliome v1.512 ARF3 Dean Phelan reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36369169, 34346499; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), ARF3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.512 GABRA3 Zornitza Stark Classified gene: GABRA3 as Green List (high evidence)
Mendeliome v1.512 GABRA3 Zornitza Stark Gene: gabra3 has been classified as Green List (High Evidence).
Mendeliome v1.511 DCLRE1B Manny Jacobs reviewed gene: DCLRE1B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 10699141, 20479256, 35007328; Phenotypes: Dyskeratosis congenita, autosomal recessive 8; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.511 NPC1 Naomi Baker gene: NPC1 was added
gene: NPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 36417180
Phenotypes for gene: NPC1 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: NPC1 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.511 EMILIN1 Zornitza Stark Publications for gene: EMILIN1 were set to PMID: 31978608; 26462740.
Mendeliome v1.510 EMILIN1 Zornitza Stark Phenotypes for gene: EMILIN1 were changed from Neuronopathy, distal hereditary motor, type X, MIM# 620080 to Neuronopathy, distal hereditary motor, type X, MIM# 620080; Aortic aneurysm, MONDO:0005160, EMILIN2-related
Mendeliome v1.509 EMILIN1 Zornitza Stark Mode of inheritance for gene: EMILIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.508 EMILIN1 Zornitza Stark Classified gene: EMILIN1 as Green List (high evidence)
Mendeliome v1.508 EMILIN1 Zornitza Stark Gene: emilin1 has been classified as Green List (High Evidence).
Mendeliome v1.507 EMILIN1 Karina Sandoval reviewed gene: EMILIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36351433; Phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080, Peripheral neuropathy, aortic aneurysm; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.507 GABRA3 Sarah Pantaleo gene: GABRA3 was added
gene: GABRA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRA3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: GABRA3 were set to PMID: 29053855
Phenotypes for gene: GABRA3 were set to Epilepsy, intellectual disability, dysmorphic features,
Penetrance for gene: GABRA3 were set to Incomplete
Review for gene: GABRA3 was set to GREEN
Added comment: Six variants in GABRA3 encoding the alpha3-subunit of the GABA(A) receptor.
Five missense variants and one micro duplication were detected in four families and two sporadic cases presenting with a range of epileptic seizure types, a varying degree of intellectual disability and developmental delay, sometimes with dysmorphic features or nystagmus.
The variants co-segregated mostly but not completely with the phenotype in the families, indicating in some cases incomplete penetrance, involvement of other genes, or presence of phenocopies.
Overall, males were more severely affected and there were three asymptomatic female mutation carriers compared to only one male without a clinical phenotype.
Mechanism suggested - three detected missense variants are localised in the extracellular GABA-binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane segment of the alpha3-subunit. Functional studies in Xenopus leaves oocytes revealed a variable but significant reduction of GABA-evoked anion currents for all mutants compared to wild-type receptors. The degree of current reduction correlated partially with the phenotype.
Results reveal that rare loss-of-function variants in GABRA3 increase the risk for a varying combination of epilepsy, intellectual disability/developmental delay and dysmorphic features, presenting in some pedigrees with an X-linked inheritance pattern.
Sources: Literature
Mendeliome v1.507 TCEAL1 Zornitza Stark Marked gene: TCEAL1 as ready
Mendeliome v1.507 TCEAL1 Zornitza Stark Gene: tceal1 has been classified as Green List (High Evidence).
Mendeliome v1.507 TCEAL1 Zornitza Stark Phenotypes for gene: TCEAL1 were changed from hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features. to Neurodevelopmental disorder, MONDO:0700092, TCEAL1-related; hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features.
Mendeliome v1.506 TCEAL1 Zornitza Stark Classified gene: TCEAL1 as Green List (high evidence)
Mendeliome v1.506 TCEAL1 Zornitza Stark Gene: tceal1 has been classified as Green List (High Evidence).
Mendeliome v1.505 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.505 SHROOM4 Alison Yeung Classified gene: SHROOM4 as Green List (high evidence)
Mendeliome v1.505 SHROOM4 Alison Yeung Gene: shroom4 has been classified as Green List (High Evidence).
Mendeliome v1.504 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 TCEAL1 Melanie Marty changed review comment from: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature; to: 7 individuals (males and females) with de novo variants involving TCEAL1 with an X-linked
dominant neurodevelopmental syndrome. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 SHROOM4 Alison Yeung reviewed gene: SHROOM4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36379543, 35663265; Phenotypes: Congenital anomaly of the kidney and urinary tracy (CAKUT), SHROOM4-related, MONDO:0019719, epilepsy, idiopathic generalised, SHROOM4-related, MONDO:0005579; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.504 UQCRH Chern Lim gene: UQCRH was added
gene: UQCRH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UQCRH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCRH were set to 34750991
Phenotypes for gene: UQCRH were set to Mitochondrial complex III deficiency, nuclear type 11, MIM#620137
Review for gene: UQCRH was set to AMBER
gene: UQCRH was marked as current diagnostic
Added comment: PMID: 34750991:
- Two affected cousins, presented with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycaemia and encephalopathy.
- Both have a 2.2 kb homozygous deletion of exons 2 and 3 of UQCRH, predicted to culminate in an in-frame deletion exons 2 and 3 of the four-exon UQCRH gene, resulting in a shortened product.
- Mouse model with the equivalent homozygous Uqcrh deletion (Uqcrh-/-) also presented with lactic acidosis and hyperammonaemia, but had a more severe, non-episodic phenotype, resulting in failure to thrive and early death.
- Patient fibroblasts and Uqcrh-/- mouse tissues showed a CIII defect.
- Expression of wild-type UQCRH in patient fibroblasts ameliorates the CIII defect.
Sources: Literature
Mendeliome v1.504 FEM1C Paul De Fazio gene: FEM1C was added
gene: FEM1C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FEM1C were set to 36336956; 28135719; 33398170; 33398168
Phenotypes for gene: FEM1C were set to Neurodevelopmental disorder, FEM1C-related MONDO:0700092
Review for gene: FEM1C was set to GREEN
gene: FEM1C was marked as current diagnostic
Added comment: PMID:36336956 describes a 9-year-old boy with severe DD, lack of speech, pyramidal signs, and limb ataxia who had a de novo missense variant Asp126His in FEM1C ascertained by WES. The equivalent variant introduced into the nematode C.elegans resulted in disabled locomotion caused by synaptic abnormalities and not muscle dysfunction.

An alternate change Asp126Val was reported in the DDD study de novo in a patient with uncharacterised developmental delay (PMID:28135719).

The Asp126 residue (but not either of the variants above specifically) was shown to be functionally important by in vitro studies (PMID:33398170;33398168). The residue is highly conserved and located in a region of missense constraint.

Borderline green, 2 patients and an animal model. Note all evidence points to the Asp126 residue being of specific importance.
Sources: Literature
Mendeliome v1.504 TCEAL1 Melanie Marty gene: TCEAL1 was added
gene: TCEAL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TCEAL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TCEAL1 were set to PMID: 36368327
Phenotypes for gene: TCEAL1 were set to hypotonia, abnormal gait, developmental delay, intellectual disability, autism, dysmorphic facial features.
Review for gene: TCEAL1 was set to GREEN
Added comment: 7 individuals (males and females) with de novo variants involving TCEAL1. Individuals had hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features included strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies.

1 additional male individual with a maternally inherited missense variant (unaffected mother), which was considered a VUS. This individual had hypertonia and spasticity without syndromic features.

4 PTCs, 2 CNVs, 2 missense reported.
Sources: Literature
Mendeliome v1.504 KDM2B Ain Roesley changed review comment from: 27 individuals from 22 families were recruited
12 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature; to: 27 individuals from 22 families were recruited
13 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature
Mendeliome v1.504 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Mendeliome v1.504 KDM2B Ain Roesley Classified gene: KDM2B as Green List (high evidence)
Mendeliome v1.504 KDM2B Ain Roesley Gene: kdm2b has been classified as Green List (High Evidence).
Mendeliome v1.503 MAN2A2 Zornitza Stark Gene: man2a2 has been classified as Red List (Low Evidence).
Mendeliome v1.503 KDM2B Ain Roesley gene: KDM2B was added
gene: KDM2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to 36322151
Phenotypes for gene: KDM2B were set to neurodevelopmental disorder MONDO#070009, KDM2B-related
Review for gene: KDM2B was set to GREEN
gene: KDM2B was marked as current diagnostic
Added comment: 27 individuals from 22 families were recruited
12 SNV classified LP/P, all de novo except 2 familial cases
5 variants were classified as VUS if more than 1 het is present in gnomAD or does result in a KDM2B-specific episignature (therefore suggesting normal function)
Sources: Literature
Mendeliome v1.502 MAN2A2 Zornitza Stark gene: MAN2A2 was added
gene: MAN2A2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2A2 were set to 36357165
Phenotypes for gene: MAN2A2 were set to Congenital disorder of glycosylation, MONDO:0015286, MAN2A2-reated
Review for gene: MAN2A2 was set to RED
Added comment: Single consanguineous family reported with homozygous truncating variant in two brothers with ID. Supportive biochemical data only.
Sources: Literature
Mendeliome v1.501 ARPC4 Zornitza Stark Phenotypes for gene: ARPC4 were changed from Neurodevelopmental disorder, ARPC4-related MONDO#0700092 to Developmental delay, language impairment, and ocular abnormalities, MIM# 620141
Mendeliome v1.500 ARPC4 Zornitza Stark edited their review of gene: ARPC4: Changed phenotypes: Developmental delay, language impairment, and ocular abnormalities, MIM# 620141
Mendeliome v1.500 MLIP Zornitza Stark Phenotypes for gene: MLIP were changed from MLIP-related myopathy with rhabdomyolysis to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Mendeliome v1.499 MLIP Zornitza Stark reviewed gene: MLIP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.499 UBE3C Zornitza Stark Gene: ube3c has been classified as Green List (High Evidence).
Mendeliome v1.499 UBE3C Zornitza Stark Phenotypes for gene: UBE3C were changed from Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM# to Neurodevelopmental disorder, MONDO:0700092, UBE3C-related
Mendeliome v1.498 UBE3C Zornitza Stark reviewed gene: UBE3C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, UBE3C-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.498 KIF26A Zornitza Stark Gene: kif26a has been classified as Green List (High Evidence).
Mendeliome v1.498 KIF26A Zornitza Stark Phenotypes for gene: KIF26A were changed from Congenital brain malformations, no OMIM # to Cerebral malformation MONDO:0016054, KIF26-related
Mendeliome v1.497 KIF26A Zornitza Stark reviewed gene: KIF26A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral malformation MONDO:0016054, KIF26-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.497 BMP6 Zornitza Stark Phenotypes for gene: BMP6 were changed from Iron overload, mild to moderate to {Iron overload, susceptibility to} 620121
Mendeliome v1.496 BMP6 Zornitza Stark edited their review of gene: BMP6: Changed phenotypes: {Iron overload, susceptibility to} 620121
Mendeliome v1.496 UBE3C Chirag Patel Classified gene: UBE3C as Green List (high evidence)
Mendeliome v1.496 UBE3C Chirag Patel Gene: ube3c has been classified as Green List (High Evidence).
Mendeliome v1.495 UBE3C Chirag Patel gene: UBE3C was added
gene: UBE3C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBE3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3C were set to PMID: 36401616
Phenotypes for gene: UBE3C were set to Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM#
Review for gene: UBE3C was set to GREEN
Added comment: 3 patients/2 families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. WES found bi-allelic variants in UBE3C. The RNA studies in some patients with LoF variants provided evidence for the LoF effect.
Sources: Literature
Mendeliome v1.494 HECTD4 Chirag Patel Classified gene: HECTD4 as Green List (high evidence)
Mendeliome v1.494 HECTD4 Chirag Patel Gene: hectd4 has been classified as Green List (High Evidence).
Mendeliome v1.493 HECTD4 Chirag Patel gene: HECTD4 was added
gene: HECTD4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to PMID: 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder overlapping Angelman syndrome, no OMIM#
Review for gene: HECTD4 was set to GREEN
Added comment: 7 patients/5 families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. WES found bi-allelic variants in HECTD4. The RNA studies in some patients with LoF variants provided evidence for the LoF effect.
Sources: Literature
Mendeliome v1.492 KIF26A Chirag Patel Classified gene: KIF26A as Green List (high evidence)
Mendeliome v1.492 KIF26A Chirag Patel Gene: kif26a has been classified as Green List (High Evidence).
Mendeliome v1.491 KIF26A Chirag Patel gene: KIF26A was added
gene: KIF26A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to PMID: 36228617
Phenotypes for gene: KIF26A were set to Congenital brain malformations, no OMIM #
Review for gene: KIF26A was set to GREEN
Added comment: 5 unrelated patients with biallelic loss-of-function variants in KIF26A (found through WES), exhibiting a spectrum of congenital brain malformations (schizencephaly, corpus callosum anomalies, polymicrgyria, and ventriculomegaly). Combining mice and human iPSC-derived organoid models, they discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA sequencing in KIF26A knockout organoids revealed transcriptional changes in MAPK, MYC, and E2F pathways.
Sources: Literature
Mendeliome v1.490 TAMM41 Zornitza Stark Phenotypes for gene: TAMM41 were changed from inborn mitochondrial metabolism disorder MONDO:0004069; hypotonia; developmental delay; myopathy; ptosis to Combined oxidative phosphorylation deficiency-56 (COXPD56), MIM#620139; hypotonia; developmental delay; myopathy; ptosis
Mendeliome v1.489 TAMM41 Zornitza Stark reviewed gene: TAMM41: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency-56 (COXPD56), MIM#620139; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.489 PIGN Zornitza Stark edited their review of gene: PIGN: Added comment: Large cohort study of 21 new and review of 40 previously published cases in PMID 36322149

Biallelic-truncating variants were detected in 16 patients-10 with Fryns syndrome, 1 with MCAHS1, 2 with Fryns syndrome/MCAHS1, and 3 with neurologic phenotype. There was an increased risk of prenatal or neonatal death within this group (6 deaths were in utero or within 2 months of life; 6 pregnancies were terminated). Incidence of polyhydramnios, congenital anomalies (eg, diaphragmatic hernia), and dysmorphism was significantly increased. Biallelic missense or mixed genotype were reported in the remaining 45 cases-32 showed a neurologic phenotype and 12 had MCAHS1. No cases of diaphragmatic hernia or abdominal wall defects were seen in this group except patient 1 in which we found the missense variant p.Ser893Arg to result in functionally null alleles, suggesting the possibility of an undescribed functionally important region in the final exon.; Changed publications: 36322149; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563, Fryns syndrome
Mendeliome v1.489 PIGN Zornitza Stark Phenotypes for gene: PIGN were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563 to Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563; Fryns syndrome
Mendeliome v1.488 SPTAN1 Zornitza Stark Publications for gene: SPTAN1 were set to 20493457; 22258530; 32811770; 33578420; 31332438
Mendeliome v1.487 SPTAN1 Zornitza Stark Mode of inheritance for gene: SPTAN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.486 SPTAN1 Zornitza Stark edited their review of gene: SPTAN1: Added comment: PMID 36331550: further 31 individuals reported with mono-allelic variants. Three phenotypes observed:
1. DEE
2. Isolated DD/ID
3. HSP or ataxia; Changed publications: 20493457, 22258530, 32811770, 35150594, 34526651, 31515523, 36331550
Mendeliome v1.486 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.486 SEC16B Zornitza Stark Classified gene: SEC16B as Amber List (moderate evidence)
Mendeliome v1.486 SEC16B Zornitza Stark Gene: sec16b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.485 SEC16B Zornitza Stark gene: SEC16B was added
gene: SEC16B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SEC16B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC16B were set to 28375157; 28862642; 30652979
Phenotypes for gene: SEC16B were set to Polycystic liver disease (with or without kidney cysts), MONDO:0000447, SEC16B-related
Review for gene: SEC16B was set to AMBER
Added comment: Two unrelated individuals with limited supporting functional data reported. Assessed as LIMITED by ClinGen.
Sources: Expert Review
Mendeliome v1.484 ADAMTS9 Zornitza Stark Phenotypes for gene: ADAMTS9 were changed from Nephronophthisis-Related Ciliopathy to Nephropathy-related ciliopathy, MONDO:0022409, ADAMTS9-related
Mendeliome v1.483 NDUFB7 Zornitza Stark Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to Mitochondrial complex I deficiency nuclear type 39 (MC1DN39), MIM#620135; Congenital lactic acidosis; hypertrophic cardiomyopathy
Mendeliome v1.482 NDUFB7 Zornitza Stark reviewed gene: NDUFB7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency nuclear type 39 (MC1DN39), MIM#620135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.482 ADAMTS9 Chirag Patel Classified gene: ADAMTS9 as Amber List (moderate evidence)
Mendeliome v1.482 ADAMTS9 Chirag Patel Gene: adamts9 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.481 ADAMTS9 Chirag Patel reviewed gene: ADAMTS9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.481 KCNJ16 Zornitza Stark Phenotypes for gene: KCNJ16 were changed from Renal tubulopathy; deafness to Inherited renal tubular disease, MONDO:0015962, KCNJ16-related; Renal tubulopathy; deafness
Mendeliome v1.480 KCNJ16 Zornitza Stark edited their review of gene: KCNJ16: Changed phenotypes: Inherited renal tubular disease, MONDO:0015962, KCNJ16-related, Renal tubulopathy, deafness
Mendeliome v1.480 MYCN Zornitza Stark reviewed gene: MYCN: Rating: RED; Mode of pathogenicity: None; Publications: 34590686; Phenotypes: cleft lip with or without cleft palate, MONDO:0016034, MYCN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.480 AFDN Zornitza Stark Gene: afdn has been classified as Red List (Low Evidence).
Mendeliome v1.480 AFDN Zornitza Stark gene: AFDN was added
gene: AFDN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AFDN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFDN were set to 36384317
Phenotypes for gene: AFDN were set to Cleft lip/palate, MONDO:0016044, AFDN-related
Review for gene: AFDN was set to RED
Added comment: Over-representation of rare AFDN missense variants reported in a cohort of CL/P individuals of African and Brazilian origin. However, almost all of the variants reported have hets in gnomad. The one that is novel has alternative missense at the same aa position.
Sources: Literature
Mendeliome v1.479 FOXA2 Zornitza Stark Publications for gene: FOXA2 were set to 29329447; 28973288; 11445544
Mendeliome v1.478 FOXA2 Zornitza Stark edited their review of gene: FOXA2: Added comment: PMID 33999151: two further individuals reported.; Changed publications: 29329447, 28973288, 11445544, 33999151
Mendeliome v1.478 FOXI1 Zornitza Stark Deleted their review
Mendeliome v1.478 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.478 FOXP3 Zornitza Stark Tag treatable tag was added to gene: FOXP3.
Mendeliome v1.478 CLEC3B Zornitza Stark Gene: clec3b has been classified as Green List (High Evidence).
Mendeliome v1.478 CLEC3B Zornitza Stark Classified gene: CLEC3B as Green List (high evidence)
Mendeliome v1.478 CLEC3B Zornitza Stark Gene: clec3b has been classified as Green List (High Evidence).
Mendeliome v1.477 CLEC3B Zornitza Stark Tag founder tag was added to gene: CLEC3B.
Mendeliome v1.477 CLEC3B Chirag Patel gene: CLEC3B was added
gene: CLEC3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLEC3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLEC3B were set to PMID: 35331648
Phenotypes for gene: CLEC3B were set to Macular dystrophy, retinal, 4, OMIM #619977
Review for gene: CLEC3B was set to GREEN
Added comment: 12 affected individuals from 5 multigenerational Japanese families in a small village in Miyazaki diagnosed with autosomal dominant maculoretinopathy. WES identified a pathogenic variant (p.Ala180Asp) in CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Variant cosegregated with the ocular phenotype.

Mice that received subretinal injections with CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. The optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in the mice.
Sources: Literature
Mendeliome v1.476 PDIA6 Chirag Patel edited their review of gene: PDIA6: Added comment: 2nd patient with large polycystic kidneys, death and end stage renal failure at 18 months, microcephaly, bilateral inguinal hernias, umbilical hernia, developmental delay, bilateral sensorineural hearing loss, visual impairment, steatorrhea, fibrotic changes in liver, and insulin-dependent diabetes. WGS found homozygous stop-gain variant (Tyr368*) in PDIA6. Segregation not performed.; Changed rating: AMBER; Changed publications: PMID: 35856135; Changed phenotypes: Polycystic kidney disease, infancy-onset diabetes, and microcephaly
Mendeliome v1.476 ARPC4 Zornitza Stark Phenotypes for gene: ARPC4 were changed from Microcephaly; mild motor delays; significant speech impairment to Neurodevelopmental disorder, ARPC4-related MONDO#0700092
Mendeliome v1.475 ARPC4 Zornitza Stark reviewed gene: ARPC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 35047857; Phenotypes: Neurodevelopmental disorder, ARPC4-related MONDO#0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.475 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Red List (low evidence)
Mendeliome v1.475 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Mendeliome v1.474 SPTBN5 Zornitza Stark edited their review of gene: SPTBN5: Added comment: Some of the missense variants are present at high population frequencies, not compatible with Mendelian disease. Gene is tolerant of LoF in gnomad, raising questions about the pathogenicity of the LoF variant.
Commentaries questioning gene-disease relationship PMID: 36117916; 36238261; Changed rating: RED
Mendeliome v1.474 MTSS1 Zornitza Stark Mode of inheritance for gene: MTSS1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.473 MTSS1 Zornitza Stark edited their review of gene: MTSS1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.473 MTSS1 Zornitza Stark Marked gene: MTSS1 as ready
Mendeliome v1.473 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Mendeliome v1.473 MTSS1 Zornitza Stark Classified gene: MTSS1 as Green List (high evidence)
Mendeliome v1.473 MTSS1 Zornitza Stark Gene: mtss1 has been classified as Green List (High Evidence).
Mendeliome v1.472 MTSS1 Zornitza Stark gene: MTSS1 was added
gene: MTSS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTSS1 were set to 36067766
Phenotypes for gene: MTSS1 were set to Intellectual disability, MTSS1-related (MONDO#0001071)
Review for gene: MTSS1 was set to GREEN
Added comment: Five individuals with the same heterozygous de novo variant in MTSS2 (NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing.

The individuals presented with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms.

Immunoblots of fibroblasts from two affected individuals revealed that the variant does not significantly alter MTSS2 levels. We modeled the variant in Drosophila and showed that the fly ortholog missing-in-metastasis (mim) was widely expressed in most neurons and a subset of glia of the CNS. Loss of mim led to a reduction in lifespan, impaired locomotor behavior, and reduced synaptic transmission in adult flies. Expression of the human MTSS2 reference cDNA rescued the mim loss-of-function (LoF) phenotypes, whereas the c.2011C>T variant had decreased rescue ability compared to the reference, suggesting it is a partial LoF allele. However, elevated expression of the variant, but not the reference MTSS2 cDNA, led to similar defects as observed by mim LoF, suggesting that the variant is toxic and may act as a dominant-negative allele when expressed in flies.
Sources: Literature
Mendeliome v1.471 TPR Zornitza Stark Phenotypes for gene: TPR were changed from intellectual disability, MONDO:0001071; cerebellar ataxia, MONDO:0000437; microcephaly, MONDO:0001149 to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related
Mendeliome v1.470 TPR Zornitza Stark reviewed gene: TPR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.470 TPR Zornitza Stark Marked gene: TPR as ready
Mendeliome v1.470 TPR Zornitza Stark Gene: tpr has been classified as Red List (Low Evidence).
Mendeliome v1.470 TPR Zornitza Stark Classified gene: TPR as Red List (low evidence)
Mendeliome v1.470 TPR Zornitza Stark Gene: tpr has been classified as Red List (Low Evidence).
Mendeliome v1.469 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Mendeliome v1.469 SMC5 Zornitza Stark Classified gene: SMC5 as Green List (high evidence)
Mendeliome v1.469 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Mendeliome v1.468 SMC5 Zornitza Stark gene: SMC5 was added
gene: SMC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMC5 were set to 36333305
Phenotypes for gene: SMC5 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID
Review for gene: SMC5 was set to GREEN
Added comment: Four individuals from three families with a chromosome breakage disorder and bi-allelic variants in this gene. However, three of the individuals had the same homozygous missense variant. Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect. Borderline Amber/Green
Sources: Literature
Mendeliome v1.467 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Mendeliome v1.467 SLF2 Zornitza Stark Classified gene: SLF2 as Green List (high evidence)
Mendeliome v1.467 SLF2 Zornitza Stark Gene: slf2 has been classified as Green List (High Evidence).
Mendeliome v1.466 SLF2 Zornitza Stark gene: SLF2 was added
gene: SLF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLF2 were set to 36333305
Phenotypes for gene: SLF2 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID
Review for gene: SLF2 was set to GREEN
Added comment: Seven individuals from 6 families with a chromosome breakage disorder and bi-allelic variants in this gene (LoF). Functional data including zebrafish model.
Sources: Literature
Mendeliome v1.465 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to intellectual disability, MONDO:0001071; cerebellar ataxia, MONDO:0000437; microcephaly, MONDO:0001149
Review for gene: TPR was set to RED
Added comment: This gene should be added to the following diseases: Intellectual disability, microcephaly and ataxia.

Comment on classification of this gene: This gene should be added with a RED rating as the association is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Mendeliome v1.465 NF1 Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34476477; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, MONDO:0018975, renovascular hypertension, MONDO:0006947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.465 IRF2BP2 Zornitza Stark Publications for gene: IRF2BP2 were set to 27016798
Mendeliome v1.464 IRF2BP2 Zornitza Stark Classified gene: IRF2BP2 as Green List (high evidence)
Mendeliome v1.464 IRF2BP2 Zornitza Stark Gene: irf2bp2 has been classified as Green List (High Evidence).
Mendeliome v1.463 IRF2BP2 Zornitza Stark edited their review of gene: IRF2BP2: Added comment: Reports of additional patients: 4yo with chronic diarrhea, severe eczema, anemia, failure to thrive, fevers, short stature, recurrent infections, cataracts, hypodontia, hypotrichosis alopecia, hypogammaglobulinemia. The 33-year-old male presented with recurrent respiratory infections since childhood, colitis and RA beginning at age 25 years.; Changed rating: GREEN; Changed publications: 27016798, 32048120, 36193988, 33864888; Changed phenotypes: Immunodeficiency, common variable, 14, MIM# 617765
Mendeliome v1.463 MAST3 Zornitza Stark Phenotypes for gene: MAST3 were changed from Developmental and epileptic encephalopathy to Developmental and epileptic encephalopathy 108, MIM#620115
Mendeliome v1.462 MAST3 Zornitza Stark edited their review of gene: MAST3: Changed phenotypes: Developmental and epileptic encephalopathy 108, MIM#620115
Mendeliome v1.462 ATP5F1 Zornitza Stark Marked gene: ATP5F1 as ready
Mendeliome v1.462 ATP5F1 Zornitza Stark Gene: atp5f1 has been classified as Red List (Low Evidence).
Mendeliome v1.462 ATP5F1 Zornitza Stark gene: ATP5F1 was added
gene: ATP5F1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP5F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5F1 were set to 36239646
Phenotypes for gene: ATP5F1 were set to Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation-2 (HUMOP2), MIM#620085
Review for gene: ATP5F1 was set to RED
Added comment: Identical twins reported with a de novo missense variant in this gene and hyper metabolism: normal thyroid function, hyperphagia, tachypnea, increased basal temperature, and increased sweating. Biochemical studies demonstrated increased mitochondrial oxygen consumption with inefficient production of ATP in the final steps of oxidative phosphorylation due to an uncoupling defect
Sources: Expert list
Mendeliome v1.461 DUOX2 Zornitza Stark Classified gene: DUOX2 as Green List (high evidence)
Mendeliome v1.461 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Mendeliome v1.460 DOCK8 Zornitza Stark Tag treatable tag was added to gene: DOCK8.
Mendeliome v1.460 DNMT3B Zornitza Stark Tag treatable tag was added to gene: DNMT3B.
Mendeliome v1.460 CACNA1I Zornitza Stark Phenotypes for gene: CACNA1I were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with variable intellectual disability and speech impairment, with or without seizures (NEDISS), MIM#620114
Mendeliome v1.459 CACNA1I Zornitza Stark reviewed gene: CACNA1I: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with variable intellectual disability and speech impairment, with or without seizures (NEDISS), MIM#620114; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.459 RPS6KB1 Arina Puzriakova gene: RPS6KB1 was added
gene: RPS6KB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPS6KB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPS6KB1 were set to 34916228
Phenotypes for gene: RPS6KB1 were set to Hypertrophic cardiomyopathy
Review for gene: RPS6KB1 was set to GREEN
Added comment: Jain et al. 2022 (PMID: 34916228) reported on two unrelated HCM families with the same heterozygous missense RPS6KB1 variant (p.G47W), and subsequently three further unrelated probands with HCM harbouring distinct heterozygous variants (p.Q49K, p.Y62H, respectively). Variants segregated with disease, were predicted pathogenic by silico analyses and were ultrarare or absent in population databases. Functional studies in the HL-1 (mouse cardiomyocytes) cells showed that the patient-specific RPS6KB1 mutant significantly increased cell size and activated rpS6 and ERK1/2 signalling cascades. The relationship between RPS6KB1 and cardiac hypertrophy has also been explored in feline and mice models (PMID: 15226426; 17976640)
Sources: Literature
Mendeliome v1.459 HK1 Zornitza Stark Tag deep intronic tag was added to gene: HK1.
Mendeliome v1.459 HK1 Zornitza Stark edited their review of gene: HK1: Added comment: PMID 36333503: 14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1) identified in individuals with hyperinsulinism.; Changed publications: 19536174, 30778173, 25316723, 25190649, 31621442, 32814480, 7655856, 12393545, 33361148, 31119733, 27282571, 36333503; Changed phenotypes: Hyperinsulinism MONDO:0002177, HK1-related, Neuropathy, hereditary motor and sensory, Russe type , MIM#605285, Haemolytic anaemia due to hexokinase deficiency, MIM# 235700, Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547, Retinitis pigmentosa 79, MIM# 617460
Mendeliome v1.459 FRA10AC1 Zornitza Stark Phenotypes for gene: FRA10AC1 were changed from Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Mendeliome v1.458 FRA10AC1 Zornitza Stark edited their review of gene: FRA10AC1: Changed phenotypes: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Mendeliome v1.458 ITPR3 Zornitza Stark Phenotypes for gene: ITPR3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111
Mendeliome v1.457 ITPR3 Zornitza Stark Publications for gene: ITPR3 were set to 32949214
Mendeliome v1.456 ITPR3 Zornitza Stark Classified gene: ITPR3 as Green List (high evidence)
Mendeliome v1.456 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Green List (High Evidence).
Mendeliome v1.455 ITPR3 Zornitza Stark edited their review of gene: ITPR3: Added comment: Additional family with 3 individuals in 2 generations reported in PMID 24627108.; Changed rating: GREEN; Changed publications: 32949214, 24627108; Changed phenotypes: Charcot-Marie-Tooth disease, demyelinating, type 1J, MIM# 620111
Mendeliome v1.455 THAP1 Zornitza Stark Publications for gene: THAP1 were set to 21793105; 22377579
Mendeliome v1.454 THAP1 Zornitza Stark Mode of inheritance for gene: THAP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.453 WDR5 Bryony Thompson Gene: wdr5 has been classified as Green List (High Evidence).
Mendeliome v1.453 WDR5 Bryony Thompson Classified gene: WDR5 as Green List (high evidence)
Mendeliome v1.453 WDR5 Bryony Thompson Gene: wdr5 has been classified as Green List (High Evidence).
Mendeliome v1.452 WDR5 Bryony Thompson gene: WDR5 was added
gene: WDR5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100157
Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder MONDO:0700092, WDR5-related
Mode of pathogenicity for gene: WDR5 was set to Other
Review for gene: WDR5 was set to GREEN
Added comment: Six different missense variants were identified (de novo) in 11 affected individuals with neurodevelopmental disorders, with a broad spectrum of additional features, including epilepsy, aberrant growth parameters, skeletal and cardiac abnormalities. In vivo and in vitro functional suggest that loss-of-function is not the mechanism of disease. The mechanism of disease is yet to be established.
Sources: Literature
Mendeliome v1.451 TOMM7 Bryony Thompson edited their review of gene: TOMM7: Changed publications: 36299998
Mendeliome v1.451 KPNA3 Zornitza Stark Phenotypes for gene: KPNA3 were changed from Hereditary Spastic Paraplegia, infantile onset to Spastic paraplegia-88 (SPG88), MIM#620106
Mendeliome v1.450 KPNA3 Zornitza Stark reviewed gene: KPNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia-88 (SPG88), MIM#620106; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.450 JARID2 Zornitza Stark Phenotypes for gene: JARID2 were changed from Intellectual disability to Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF), MIM#620098
Mendeliome v1.449 JARID2 Zornitza Stark edited their review of gene: JARID2: Changed phenotypes: Developmental delay with variable intellectual disability and dysmorphic facies (DIDDF), MIM#620098
Mendeliome v1.449 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from Cutis laxa, intellectual disability, movement disorder to complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516; Cutis laxa, intellectual disability, movement disorder
Mendeliome v1.448 PI4K2A Zornitza Stark Publications for gene: PI4K2A were set to 32418222
Mendeliome v1.447 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Green List (High Evidence).
Mendeliome v1.447 DNAJB4 Zornitza Stark Classified gene: DNAJB4 as Green List (high evidence)
Mendeliome v1.447 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Green List (High Evidence).
Mendeliome v1.446 DNAJB4 Karina Sandoval gene: DNAJB4 was added
gene: DNAJB4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJB4 were set to PMID: 36264506
Phenotypes for gene: DNAJB4 were set to Myopathy, MONDO:0005336, DNAJB4-related
Review for gene: DNAJB4 was set to GREEN
Added comment: 4 individuals from 3 unrelated families with bi-allelic LoF/missense variants in this gene, and either childhood/adult onset of muscle weakness and respiratory failure. One had HCM.

Functional studies including mouse model.
Sources: Literature
Mendeliome v1.446 ATP11A Zornitza Stark Publications for gene: ATP11A were set to PMID: 34403372; 35278131
Mendeliome v1.445 ATP11A Zornitza Stark edited their review of gene: ATP11A: Changed phenotypes: Leukodystrophy, hypomyelinating, 24 , MIM# 619851, Deafness, autosomal dominant 84 (MIM#619810)
Mendeliome v1.445 ATP11A Chern Lim reviewed gene: ATP11A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36300302; Phenotypes: Deafness, autosomal dominant 84 (MIM#619810); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.445 PI4K2A Seb Lunke Classified gene: PI4K2A as Green List (high evidence)
Mendeliome v1.445 PI4K2A Seb Lunke Gene: pi4k2a has been classified as Green List (High Evidence).
Mendeliome v1.444 PI4K2A Seb Lunke reviewed gene: PI4K2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30564627, 35880319, 19581584; Phenotypes: complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.444 MYCBP2 Zornitza Stark Gene: mycbp2 has been classified as Green List (High Evidence).
Mendeliome v1.444 MYCBP2 Zornitza Stark Classified gene: MYCBP2 as Green List (high evidence)
Mendeliome v1.444 MYCBP2 Zornitza Stark Gene: mycbp2 has been classified as Green List (High Evidence).
Mendeliome v1.443 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Mendeliome v1.443 CAMSAP1 Zornitza Stark Classified gene: CAMSAP1 as Green List (high evidence)
Mendeliome v1.443 CAMSAP1 Zornitza Stark Gene: camsap1 has been classified as Green List (High Evidence).
Mendeliome v1.442 THAP1 Michelle Torres commented on gene: THAP1: Monoallelic is well established with reduced penetrance.

Biallelic was seen in 3 families generally with severe and early onset dystonia:

PMID: 36205328: consanguineous family (gene panel), proband homozygous for p.Lys162Asn with early onset multifocal dystonia with severe oromandibular/laryngeal dysfunction; both parents were confirmed carriers with milder features (47 yo father with tightness and difficulty with fine motor tasks, 41 yo mother with tightness).

PMID: 21425335: 3 siblings are homozygous for the p.Leu32His with early-onset generalized dystonia. Carriers were unaffected.

PMID: 20211909: a homozygous variant was identified in an individual with with writer's dystonia initially and then developing segmental dystonia, onset at 57 yo, parents could not be tested.
Mendeliome v1.442 CAMSAP1 Naomi Baker gene: CAMSAP1 was added
gene: CAMSAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related
Review for gene: CAMSAP1 was set to GREEN
Added comment: Five unrelated families with bi-allelic loss-of-function variants. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe neurodevelopmental delay, cortical visual impairment, and seizures.
Sources: Literature
Mendeliome v1.442 THAP1 Michelle Torres reviewed gene: THAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36205328, 21425335, 20211909; Phenotypes: Dystonia 6, torsion, (MIM#60262); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.442 MYCBP2 Suliman Khan gene: MYCBP2 was added
gene: MYCBP2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYCBP2 were set to PMID: 36200388
Phenotypes for gene: MYCBP2 were set to Neurodevelopmental disorder, MONDO:0700092, MYCBP2-related; corpus callosum abnormalities
Penetrance for gene: MYCBP2 were set to Complete
Review for gene: MYCBP2 was set to GREEN
Added comment: PMID: 36200388 reported eight patients with neurodevelopmental disorder including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy, and autistic features. Each patient harbored a de novo LOF variant in MYCBP2 gene. Functional study supported a direct link between MYCBP2 and neurodevelopmental spectrum disorder specifically corpus callosum defects.
Sources: Literature
Mendeliome v1.442 KLHL20 Zornitza Stark Gene: klhl20 has been classified as Green List (High Evidence).
Mendeliome v1.442 KLHL20 Zornitza Stark Classified gene: KLHL20 as Green List (high evidence)
Mendeliome v1.442 KLHL20 Zornitza Stark Gene: klhl20 has been classified as Green List (High Evidence).
Mendeliome v1.441 KLHL20 Dean Phelan gene: KLHL20 was added
gene: KLHL20 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL20 were set to PMID: 36214804
Phenotypes for gene: KLHL20 were set to Neurodevelopmental disorder (MONDO:0700092), KLHL20-related
Review for gene: KLHL20 was set to GREEN
Added comment: PMID: 36214804
- 14 patients with de novo missense variants in KLHL20. The patients had mild to severe ID, febrile seizures or epilepsy, autism spectrum disorder, hyperactivity and subtle dysmorphic facial features.
Sources: Literature
Mendeliome v1.441 FICD Alison Yeung Gene: ficd has been classified as Green List (High Evidence).
Mendeliome v1.441 FICD Alison Yeung Classified gene: FICD as Green List (high evidence)
Mendeliome v1.441 FICD Alison Yeung Gene: ficd has been classified as Green List (High Evidence).
Mendeliome v1.440 FICD Alison Yeung gene: FICD was added
gene: FICD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FICD were set to 36136088
Phenotypes for gene: FICD were set to Hereditary motor neurone disease, FICD-related, MONDO:0024257
Review for gene: FICD was set to GREEN
Added comment: Three unrelated families with recurrent homozygous missense variant: p.Arg374His
One further family with Chet variants: p.Arg 374His and p.Gly370GlufsTer53

Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP.

Onset of symptoms in childhood with progressive course. Presentation with severe lower limb spasticity and mild upper limb spascticity, nerve conduction test shows motor neuropathy.
Sources: Literature
Mendeliome v1.439 METTL23 Lucy Spencer reviewed gene: METTL23: Rating: AMBER; Mode of pathogenicity: None; Publications: 36099048; Phenotypes: glaucoma MONDO:0005041; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.439 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Mendeliome v1.439 FOXI3 Zornitza Stark Mode of inheritance for gene: FOXI3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.438 FOXI3 Zornitza Stark Classified gene: FOXI3 as Green List (high evidence)
Mendeliome v1.438 FOXI3 Zornitza Stark Gene: foxi3 has been classified as Green List (High Evidence).
Mendeliome v1.437 FOXI3 Paul De Fazio gene: FOXI3 was added
gene: FOXI3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXI3 were set to 36260083
Phenotypes for gene: FOXI3 were set to Dysostosis with predominant craniofacial involvement (MONDO:0800085)
Penetrance for gene: FOXI3 were set to Incomplete
Review for gene: FOXI3 was set to GREEN
gene: FOXI3 was marked as current diagnostic
Added comment: Ten affected individuals from 4 families reported with monoallelic variants, 2 with missense variants affecting the nuclear localisation sequence and 2 with frameshift variants.

The missense variants were associated with isolated microtia with aural atresia and affected subcellular localisation of the protein, while the frameshift variants were associated with microtia and mandubular hypoplasia, suggesting dosage sensitivity.

Rated green but CAUTION for incomplete penetrance. 3 of the 4 families had unaffected carriers. Family 1 in particular had 25 genotyped individuals, of which 15 were carriers, of which 5 were affected.
Sources: Literature
Mendeliome v1.437 TOMM7 Zornitza Stark Publications for gene: TOMM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100148
Mendeliome v1.436 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Changed publications: 36299998, 36282599
Mendeliome v1.436 TOMM7 Zornitza Stark edited their review of gene: TOMM7: Added comment: Second family reported in PMID 36282599: single affected individual with homozygous missense variant; clinical presentation with progeroid features but functional data supports underlying mitochondrial aetiology.

Maintain Amber rating as the two patients have quite disparate clinical presentations.; Changed publications: 36282599
Mendeliome v1.436 CBFB Ain Roesley Gene: cbfb has been classified as Green List (High Evidence).
Mendeliome v1.436 CBFB Ain Roesley Classified gene: CBFB as Green List (high evidence)
Mendeliome v1.436 CBFB Ain Roesley Gene: cbfb has been classified as Green List (High Evidence).
Mendeliome v1.435 CBFB Ain Roesley gene: CBFB was added
gene: CBFB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBFB were set to 36241386
Phenotypes for gene: CBFB were set to cleidocranial dysplasia (MONDO#0007340), CBFB-related
Penetrance for gene: CBFB were set to Complete
Review for gene: CBFB was set to GREEN
gene: CBFB was marked as current diagnostic
Added comment: 5 families with 8 individuals, including 2 de novos and 1 intragenic exon 4 deletion

In 1 family, the mother did not report skeletal concerns but had dental abnormalities during childhood
Sources: Literature
Mendeliome v1.434 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from Specific granule deficiency, MIM# 245480 to Specific granule deficiency, MIM# 245480; Immunodeficiency 108 with autoinflammation, MIM# 260570
Mendeliome v1.433 CEBPE Zornitza Stark Publications for gene: CEBPE were set to 10359588; 11313242; 31256937; 29651288
Mendeliome v1.432 CEBPE Zornitza Stark edited their review of gene: CEBPE: Added comment: Additional family with auto inflammatory phenotype published in 31201888, extensive functional data.; Changed publications: 10359588, 11313242, 31256937, 29651288, 31201888
Mendeliome v1.432 CEBPE Zornitza Stark edited their review of gene: CEBPE: Changed phenotypes: Specific granule deficiency, MIM# 245480, Immunodeficiency 108 with autoinflammation, MIM# 260570
Mendeliome v1.432 CXCR4 Zornitza Stark Tag treatable tag was added to gene: CXCR4.
Mendeliome v1.432 PGM1 Zornitza Stark Tag treatable tag was added to gene: PGM1.
Mendeliome v1.432 SFTPA1 Zornitza Stark Publications for gene: SFTPA1 were set to 31601679; 30854216; 28869238; 26792177
Mendeliome v1.431 SFTPA1 Zornitza Stark Classified gene: SFTPA1 as Green List (high evidence)
Mendeliome v1.431 SFTPA1 Zornitza Stark Gene: sftpa1 has been classified as Green List (High Evidence).
Mendeliome v1.430 SFTPA1 Zornitza Stark edited their review of gene: SFTPA1: Added comment: Additional 3 families reported with mono-allelic variants.; Changed rating: GREEN; Changed publications: 31601679, 30854216, 28869238, 26792177, 32855221
Mendeliome v1.430 GNPNAT1 Krithika Murali reviewed gene: GNPNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36097642, 35427807; Phenotypes: Rhizomelic dysplasia, Ain-Naz type, MIM#619598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.430 SCNM1 Zornitza Stark Phenotypes for gene: SCNM1 were changed from Ciliopathy, SCNM1-related, MONDO:0005308 to Orofaciodigital syndrome XIX, MIM# 620107
Mendeliome v1.429 SCNM1 Zornitza Stark reviewed gene: SCNM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome XIX, MIM# 620107; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.429 FRMD5 Zornitza Stark Phenotypes for gene: FRMD5 were changed from Neurodevelopmental disorder MONDO:0700092, FRMD5-related to Neurodevelopmental disorder with eye movement abnormalities and ataxia, MIM# 620094
Mendeliome v1.428 FRMD5 Zornitza Stark edited their review of gene: FRMD5: Changed phenotypes: Neurodevelopmental disorder with eye movement abnormalities and ataxia, MIM# 620094
Mendeliome v1.428 FGL2 Zornitza Stark Gene: fgl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.428 FGL2 Zornitza Stark Classified gene: FGL2 as Amber List (moderate evidence)
Mendeliome v1.428 FGL2 Zornitza Stark Gene: fgl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.427 FGL2 Zornitza Stark gene: FGL2 was added
gene: FGL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FGL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGL2 were set to 36243222
Phenotypes for gene: FGL2 were set to Autoinflammatory syndrome, MONDO:0019751, FGL2-related
Review for gene: FGL2 was set to AMBER
Added comment: Child with early onset systemic inflammation, autoantibodies, and vasculitis. Homozygous truncating variant, functional studies include rescue experiments.
Sources: Literature
Mendeliome v1.426 SP6 Zornitza Stark Phenotypes for gene: SP6 were changed from hypoplastic amelogenesis imperfecta to Amelogenesis imperfecta, type IK, MIM# 620104
Mendeliome v1.425 SP6 Zornitza Stark edited their review of gene: SP6: Changed phenotypes: Amelogenesis imperfecta, type IK, MIM# 620104
Mendeliome v1.425 FKBP6 Zornitza Stark Phenotypes for gene: FKBP6 were changed from Spermatogenic failure (MONDO:0004983), FKBP6-related to Spermatogenic failure 77, MIM# 620103
Mendeliome v1.424 FKBP6 Zornitza Stark reviewed gene: FKBP6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 77, MIM# 620103; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.424 COL13A1 Zornitza Stark Tag treatable tag was added to gene: COL13A1.
Mendeliome v1.424 OTC Zornitza Stark Tag treatable tag was added to gene: OTC.
Mendeliome v1.424 RAX2 Zornitza Stark Phenotypes for gene: RAX2 were changed from Cone-rod dystrophy 11, MIM# 610381 to Cone-rod dystrophy 11, MIM# 610381; Retinitis pigmentosa-95 (RP95), MIM#620102
Mendeliome v1.423 RAX2 Zornitza Stark edited their review of gene: RAX2: Changed phenotypes: Cone-rod dystrophy 11, MIM# 610381, Retinitis pigmentosa-95 (RP95), MIM#620102
Mendeliome v1.423 LETM1 Zornitza Stark Phenotypes for gene: LETM1 were changed from Mitochondrial disease MONDO#0044970, LETM1-related to Childhood-onset neurodegeneration with multisystem involvement due to mitochondrial dysfunction (CONDMIM), MIM#620089
Mendeliome v1.422 LETM1 Zornitza Stark edited their review of gene: LETM1: Changed phenotypes: Childhood-onset neurodegeneration with multisystem involvement due to mitochondrial dysfunction (CONDMIM), MIM#620089; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.422 UNC13D Zornitza Stark Tag treatable tag was added to gene: UNC13D.
Mendeliome v1.422 PAX4 Zornitza Stark Classified gene: PAX4 as Red List (low evidence)
Mendeliome v1.422 PAX4 Zornitza Stark Gene: pax4 has been classified as Red List (Low Evidence).
Mendeliome v1.421 PAX4 Zornitza Stark Tag refuted tag was added to gene: PAX4.
Mendeliome v1.421 CLCN7 Zornitza Stark changed review comment from: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features.

Bi-allelic variants in this gene are associated with osteopetrosis.; to: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features.

Mono- and bi-allelic variants in this gene are associated with osteopetrosis.
Mendeliome v1.421 CLCN7 Zornitza Stark edited their review of gene: CLCN7: Changed phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541, Osteopetrosis, autosomal dominant 2, MIM# 166600, Osteopetrosis, autosomal recessive 4, MIM# 611490
Mendeliome v1.421 CLCN7 Zornitza Stark Tag treatable tag was added to gene: CLCN7.
Mendeliome v1.421 PAX4 Krithika Murali reviewed gene: PAX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Maturity-onset diabetes of the young, type IX - MIM#612225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.421 HNRNPH1 Zornitza Stark Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability; early onset high myopia, MONDO:0001384 to Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, MIM# 620083
Mendeliome v1.420 HNRNPH1 Zornitza Stark edited their review of gene: HNRNPH1: Changed phenotypes: Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, MIM# 620083
Mendeliome v1.420 PRDM16 Zornitza Stark Publications for gene: PRDM16 were set to 23768516; 29367541; 34915728; 31965688; 29367541
Mendeliome v1.419 PRDM16 Zornitza Stark Classified gene: PRDM16 as Green List (high evidence)
Mendeliome v1.419 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Green List (High Evidence).
Mendeliome v1.418 PRDM16 Paul De Fazio reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 29367541, 29447731, 30847666, 33082984, 32183154, 33500567, 34540771, 34350506, 34935411; Phenotypes: Cardiomyopathy, dilated, 1LL MIM#615373, Left ventricular noncompaction 8 MIM#615373; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v1.418 CD79B Zornitza Stark Tag treatable tag was added to gene: CD79B.
Mendeliome v1.418 WNK4 Zornitza Stark changed review comment from: More than 5 unrelated families reported.; to: More than 5 unrelated families reported.

Caution: assessed as MODERATE by ClinGen. Although at least 9 individuals have been reported, all the reported variants are missense without other supportive functional or segregation data.
Mendeliome v1.418 CD79A Zornitza Stark Tag treatable tag was added to gene: CD79A.
Mendeliome v1.418 CD40LG Zornitza Stark Tag treatable tag was added to gene: CD40LG.
Mendeliome v1.418 CD3E Zornitza Stark Tag treatable tag was added to gene: CD3E.
Mendeliome v1.418 CD3D Zornitza Stark Tag treatable tag was added to gene: CD3D.
Mendeliome v1.418 G6PC Zornitza Stark Tag treatable tag was added to gene: G6PC.
Mendeliome v1.418 EMILIN1 Zornitza Stark Phenotypes for gene: EMILIN1 were changed from peripheral neuropathy to Neuronopathy, distal hereditary motor, type X, MIM# 620080
Mendeliome v1.417 EMILIN1 Zornitza Stark edited their review of gene: EMILIN1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.417 EMILIN1 Zornitza Stark reviewed gene: EMILIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuronopathy, distal hereditary motor, type X, MIM# 620080; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.417 TMEM147 Zornitza Stark Phenotypes for gene: TMEM147 were changed from Neurodevelopmental disorder (MONDO:0700092), TMEM147-related to Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly, MIM# 620075
Mendeliome v1.416 TMEM147 Zornitza Stark reviewed gene: TMEM147: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly, MIM# 620075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.416 CCDC34 Zornitza Stark Gene: ccdc34 has been classified as Green List (High Evidence).
Mendeliome v1.416 CCDC34 Zornitza Stark Classified gene: CCDC34 as Green List (high evidence)
Mendeliome v1.416 CCDC34 Zornitza Stark Gene: ccdc34 has been classified as Green List (High Evidence).
Mendeliome v1.415 CCDC34 Zornitza Stark gene: CCDC34 was added
gene: CCDC34 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CCDC34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC34 were set to 34348960
Phenotypes for gene: CCDC34 were set to Spermatogenic failure 76, MIM# 620084
Review for gene: CCDC34 was set to GREEN
Added comment: Two unrelated individuals reported with homozygous frameshift variants. Mouse model recapitulated phenotype.
Sources: Expert list
Mendeliome v1.414 ACTN2 Bryony Thompson reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17097056, 20022194, 25173926, 25224718, 22767232, 27287556, 28436997, 31333075, 31956495, 32973354, 34802252, 33500567, 36078153, 36116040; Phenotypes: intrinsic cardiomyopathy MONDO:0000591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.414 CAVIN1 Zornitza Stark Tag treatable tag was added to gene: CAVIN1.
Mendeliome v1.414 NFAT5 Zornitza Stark Phenotypes for gene: NFAT5 were changed from Recurrent infections; Autoimmune enterocolopathy to Immune deficiency disease, MONDO:0003778, NFAT5-related; Recurrent infections; Autoimmune enterocolopathy; EBV susceptibility; HLH
Mendeliome v1.413 NFAT5 Zornitza Stark Publications for gene: NFAT5 were set to 25667416
Mendeliome v1.412 NFAT5 Zornitza Stark Classified gene: NFAT5 as Amber List (moderate evidence)
Mendeliome v1.412 NFAT5 Zornitza Stark Gene: nfat5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.411 NFAT5 Zornitza Stark edited their review of gene: NFAT5: Added comment: Two additional individuals with missense variants reported in PMID 36238298: one with EBV infection with hepatitis and enterocolitis, and one with fatal HLH.; Changed rating: AMBER; Changed publications: 25667416, 36238298; Changed phenotypes: Immune deficiency disease, MONDO:0003778, NFAT5-related, Recurrent infections, Autoimmune enterocolopathy, EBV susceptibility, HLH
Mendeliome v1.411 PSMC1 Zornitza Stark Phenotypes for gene: PSMC1 were changed from 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss , MIM# 620071
Mendeliome v1.410 PSMC1 Zornitza Stark edited their review of gene: PSMC1: Changed phenotypes: Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss , MIM# 620071
Mendeliome v1.410 CA2 Zornitza Stark Tag treatable tag was added to gene: CA2.
Mendeliome v1.410 LAMA5 Zornitza Stark Phenotypes for gene: LAMA5 were changed from bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay to Bent bone dysplasia syndrome 2, MIM# 620076; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Mendeliome v1.409 LAMA5 Zornitza Stark edited their review of gene: LAMA5: Changed phenotypes: Nephrotic syndrome, type 26 620049, Bent bone dysplasia syndrome 2, MIM# 620076
Mendeliome v1.409 HNRNPR Zornitza Stark Phenotypes for gene: HNRNPR were changed from Intellectual disability; seizures to Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM# 620073
Mendeliome v1.408 HNRNPR Zornitza Stark edited their review of gene: HNRNPR: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, MIM# 620073
Mendeliome v1.408 FGF14 Zornitza Stark Phenotypes for gene: FGF14 were changed from Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003 to Spinocerebellar ataxia 27, MIM# 609307; Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.407 FGF14 Zornitza Stark edited their review of gene: FGF14: Changed phenotypes: Spinocerebellar ataxia 27, MIM# 609307, Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.407 FGF14 Zornitza Stark Phenotypes for gene: FGF14 were changed from Spinocerebellar ataspinocerebellar ataxia type 27 MONDO:0012247; hereditary episodic ataxia MONDO:0016227 to Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003
Mendeliome v1.406 FGF14 Zornitza Stark reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vestibulocerebellar disorder with predominant ocular signs, MIM# 193003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.406 SCNN1A Zornitza Stark Tag treatable tag was added to gene: SCNN1A.
Mendeliome v1.406 GATA2 Zornitza Stark Tag treatable tag was added to gene: GATA2.
Mendeliome v1.406 GAMT Zornitza Stark Tag treatable tag was added to gene: GAMT.
Mendeliome v1.406 GALNS Zornitza Stark Tag treatable tag was added to gene: GALNS.
Mendeliome v1.406 IMPA1 Bryony Thompson Gene: impa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.406 IMPA1 Bryony Thompson Classified gene: IMPA1 as Amber List (moderate evidence)
Mendeliome v1.406 IMPA1 Bryony Thompson Gene: impa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.405 IMPA1 Bryony Thompson gene: IMPA1 was added
gene: IMPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IMPA1 were set to 26416544; 24554717; 32839513; 17460611
Phenotypes for gene: IMPA1 were set to intellectual disability, autosomal recessive 59 MONDO:0015020
Review for gene: IMPA1 was set to AMBER
Added comment: A homozygous frameshift variant identified in a large Brazilian consanguineous family with ID, also supporting functional studies and null mouse models.
Sources: Literature
Mendeliome v1.404 ARNT2 Bryony Thompson Marked gene: ARNT2 as ready
Mendeliome v1.404 ARNT2 Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.404 ARNT2 Bryony Thompson Classified gene: ARNT2 as Amber List (moderate evidence)
Mendeliome v1.404 ARNT2 Bryony Thompson Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.403 ARNT2 Bryony Thompson gene: ARNT2 was added
gene: ARNT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARNT2 were set to 11381139; 24022475
Phenotypes for gene: ARNT2 were set to Webb-Dattani syndrome MONDO:0014404
Review for gene: ARNT2 was set to AMBER
Added comment: A homozygous frameshift (c.1373_1374dupTC) in six affected children from a highly consanguineous family with a syndromic phenotype including microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract. In a Arnt2(-/-) mouse model embryos die perinatally and exhibit impaired hypothalamic development.
Sources: Literature
Mendeliome v1.402 HEATR3 Zornitza Stark reviewed gene: HEATR3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-Blackfan anaemia 21, MIM# 620072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.402 C6 Zornitza Stark Tag treatable tag was added to gene: C6.
Mendeliome v1.402 FAH Zornitza Stark Tag treatable tag was added to gene: FAH.
Mendeliome v1.402 ETHE1 Zornitza Stark Tag treatable tag was added to gene: ETHE1.
Mendeliome v1.402 FRMD5 Zornitza Stark Gene: frmd5 has been classified as Green List (High Evidence).
Mendeliome v1.402 FRMD5 Zornitza Stark Classified gene: FRMD5 as Green List (high evidence)
Mendeliome v1.402 FRMD5 Zornitza Stark Gene: frmd5 has been classified as Green List (High Evidence).
Mendeliome v1.401 FRMD5 Zornitza Stark gene: FRMD5 was added
gene: FRMD5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder MONDO:0700092, FRMD5-related
Review for gene: FRMD5 was set to GREEN
Added comment: Eight individuals reported with missense variants in this gene, de novo in 6 where parents were available. Clinical presentation was with ID, seizures, ataxia. Fly model.
Sources: Literature
Mendeliome v1.400 GIGYF1 Elena Savva Publications for gene: GIGYF1 were set to 33057194; 35917186
Mendeliome v1.400 GIGYF1 Elena Savva Publications for gene: GIGYF1 were set to 33057194
Mendeliome v1.399 GIGYF1 Elena Savva Phenotypes for gene: GIGYF1 were changed from Developmental disorder to Autism, Intellectual disability, GIGYF1-related (MONDO#0001071)
Mendeliome v1.398 GIGYF1 Elena Savva Classified gene: GIGYF1 as Green List (high evidence)
Mendeliome v1.398 GIGYF1 Elena Savva Gene: gigyf1 has been classified as Green List (High Evidence).
Mendeliome v1.397 GIGYF1 Elena Savva reviewed gene: GIGYF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Intellectual disability, GIGYF1-related (MONDO#0001071); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.397 TOMM7 Zornitza Stark Phenotypes for gene: TOMM7 were changed from growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy MONDO:0014911 to Inborn mitochondrial disorder MONDO:0004069, TOMM7-related
Mendeliome v1.396 TOMM7 Zornitza Stark reviewed gene: TOMM7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Inborn mitochondrial disorder MONDO:0004069, TOMM7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.396 DDC Zornitza Stark Tag treatable tag was added to gene: DDC.
Tag clinical trial tag was added to gene: DDC.
Mendeliome v1.396 DGAT1 Zornitza Stark Tag treatable tag was added to gene: DGAT1.
Mendeliome v1.396 CYP27B1 Zornitza Stark Tag treatable tag was added to gene: CYP27B1.
Mendeliome v1.396 CYP27A1 Zornitza Stark Tag treatable tag was added to gene: CYP27A1.
Mendeliome v1.396 CYP17A1 Zornitza Stark Tag treatable tag was added to gene: CYP17A1.
Mendeliome v1.396 CYP11B2 Zornitza Stark Tag treatable tag was added to gene: CYP11B2.
Mendeliome v1.396 CYP11B1 Zornitza Stark Tag treatable tag was added to gene: CYP11B1.
Mendeliome v1.396 CUBN Zornitza Stark Tag treatable tag was added to gene: CUBN.
Mendeliome v1.396 CTNS Zornitza Stark Tag treatable tag was added to gene: CTNS.
Mendeliome v1.396 CPS1 Zornitza Stark Tag treatable tag was added to gene: CPS1.
Mendeliome v1.396 TOMM7 Bryony Thompson Marked gene: TOMM7 as ready
Mendeliome v1.396 TOMM7 Bryony Thompson Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.396 TOMM7 Bryony Thompson Classified gene: TOMM7 as Amber List (moderate evidence)
Mendeliome v1.396 TOMM7 Bryony Thompson Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.395 TOMM7 Bryony Thompson gene: TOMM7 was added
gene: TOMM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to DOI:https://doi.org/10.1016/j.xhgg.2022.100148
Phenotypes for gene: TOMM7 were set to growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy MONDO:0014911
Review for gene: TOMM7 was set to AMBER
Added comment: A single case identified with a homozygous variant in TOMM7 (c.73T>C, p.Trp25Arg) that presented with syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. A mouse model of the missense variant demonstrated a bioenergetic defect and a phenotype of mitochondrial diseases. It also strongly suggested that the variant is hypomorphic because mice homozygous for this variant showed a milder phenotype than those with a homozygous Tomm7 deletion.
Sources: Literature
Mendeliome v1.394 HECW2 Bryony Thompson Mode of inheritance for gene: HECW2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.393 HECW2 Bryony Thompson reviewed gene: HECW2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35753050, 35487419; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language MONDO:0014995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.393 SEPT4 Bryony Thompson Marked gene: SEPT4 as ready
Mendeliome v1.393 SEPT4 Bryony Thompson Gene: sept4 has been classified as Green List (High Evidence).
Mendeliome v1.393 SEPT4 Bryony Thompson Classified gene: SEPT4 as Green List (high evidence)
Mendeliome v1.393 SEPT4 Bryony Thompson Gene: sept4 has been classified as Green List (High Evidence).
Mendeliome v1.392 SEPT4 Bryony Thompson gene: SEPT4 was added
gene: SEPT4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEPT4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPT4 were set to 36135717; 15737931; 15737930
Phenotypes for gene: SEPT4 were set to male infertility MONDO:0005372
Review for gene: SEPT4 was set to GREEN
Added comment: Two unrelated cases with primary male infertility (asthenoteratozoospermia) from consanguineous Chinsese families with 2 difference homozygous stopgain variants (Patient 1: c.721A>T, p.R241* and Patient 2: c.205C>T, p.R69*). Multiple supporting mouse models where the male mice are sterile.
Sources: Literature
Mendeliome v1.391 FAM20B Bryony Thompson Gene: fam20b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.391 FAM20B Bryony Thompson Classified gene: FAM20B as Amber List (moderate evidence)
Mendeliome v1.391 FAM20B Bryony Thompson Gene: fam20b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.390 FAM20B Bryony Thompson gene: FAM20B was added
gene: FAM20B was added to Mendeliome. Sources: Other
Mode of inheritance for gene: FAM20B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20B were set to 30847897; 30105814; 22732358; 27405802
Phenotypes for gene: FAM20B were set to Desbuquois dysplasia MONDO:0015426
Review for gene: FAM20B was set to AMBER
Added comment: Two siblings from a single family with neonatal short limb dysplasia resembling Desbuquois dysplasia. One of the siblings underwent genetic testing and compound heterozygous variants were identified in FAM20B ((NM_014864: c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4). Multiple mouse models reported with skeletal abnormalities.
Sources: Other
Mendeliome v1.389 EXOC6B Bryony Thompson Gene: exoc6b has been classified as Green List (High Evidence).
Mendeliome v1.389 EXOC6B Bryony Thompson Classified gene: EXOC6B as Green List (high evidence)
Mendeliome v1.389 EXOC6B Bryony Thompson Gene: exoc6b has been classified as Green List (High Evidence).
Mendeliome v1.388 EXOC6B Bryony Thompson gene: EXOC6B was added
gene: EXOC6B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOC6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC6B were set to 26669664; 30284759; 36150098
Phenotypes for gene: EXOC6B were set to Spondyloepimetaphyseal dysplasia with joint laxity MONDO:0019675
Review for gene: EXOC6B was set to GREEN
Added comment: 6 affected individuals from 4 families, and supporting assays in patient cells
PMID: 26669664 - 2 brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones from a consanguineous family, with a homozygous nonsense variant [c.906T>A/p.(Tyr302*)]
PMID: 30284759 - 2 sisters with dislocations of the hips and knees, long slender fingers with distal tapering, significant motor disability but normal (older sister) or low-normal intelligence (younger sister), with a homozygous in-frame deletion of exons 9-20
PMID: 36150098 - 2 unrelated probands from consanguineous families, one with a homozygous frameshift exon 20 deletion and one with a homozygous nonsense variant (c.401T>G p.Leu134Ter). Function assessment of patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis
Sources: Literature
Mendeliome v1.387 VPS33A Bryony Thompson Publications for gene: VPS33A were set to 28013294; 27547915
Mendeliome v1.386 VPS33A Bryony Thompson Classified gene: VPS33A as Green List (high evidence)
Mendeliome v1.386 VPS33A Bryony Thompson Gene: vps33a has been classified as Green List (High Evidence).
Mendeliome v1.385 VPS33A Bryony Thompson changed review comment from: PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells.
PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family
PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family
PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts; to: Now two missense variants reported with disease in at least 15 probands/families
PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells.
PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family
PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family
PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts
Mendeliome v1.385 DPH5 Zornitza Stark Gene: dph5 has been classified as Green List (High Evidence).
Mendeliome v1.385 DPH5 Zornitza Stark Classified gene: DPH5 as Green List (high evidence)
Mendeliome v1.385 DPH5 Zornitza Stark Gene: dph5 has been classified as Green List (High Evidence).
Mendeliome v1.384 DPH5 Zornitza Stark gene: DPH5 was added
gene: DPH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DPH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH5 were set to 35482014
Phenotypes for gene: DPH5 were set to Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, MIM# 620070
Review for gene: DPH5 was set to GREEN
Added comment: 5 individuals from 3 unrelated families reported with severe ID, feeding difficulties, dysmorphic features and congenital anomalies, though there was no consistent pattern to these.
Sources: Literature
Mendeliome v1.383 VPS33A Bryony Thompson reviewed gene: VPS33A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28013294, 27547915, 31936524, 36153662; Phenotypes: Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.383 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Intermediate CMT to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068
Mendeliome v1.382 SLC12A6 Zornitza Stark edited their review of gene: SLC12A6: Changed phenotypes: Andermann syndrome, Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800, Charcot-Marie-Tooth disease, axonal, type 2II , MIM#620068
Mendeliome v1.382 ADGRL1 Zornitza Stark Phenotypes for gene: ADGRL1 were changed from Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092) to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, MIM# 620065
Mendeliome v1.381 ADGRL1 Zornitza Stark reviewed gene: ADGRL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay, behavioral abnormalities, and neuropsychiatric disorders, MIM# 620065; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.381 VPS45 Zornitza Stark Tag treatable tag was added to gene: VPS45.
Mendeliome v1.381 XIAP Zornitza Stark Tag treatable tag was added to gene: XIAP.
Mendeliome v1.381 BRIP1 Zornitza Stark Tag treatable tag was added to gene: BRIP1.
Mendeliome v1.381 ACAD9 Zornitza Stark Tag treatable tag was added to gene: ACAD9.
Mendeliome v1.381 GALT Zornitza Stark reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactosemia MIM#230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.381 GALT Zornitza Stark Mode of inheritance for gene: GALT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.380 ACAD8 Zornitza Stark Phenotypes for gene: ACAD8 were changed from to Isobutyryl-CoA dehydrogenase deficiency MIM#611283
Mendeliome v1.379 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Cystic renal disease MONDO:0002473, ALG5-related to Polycystic kidney disease 7, MIM# 620056
Mendeliome v1.378 ALG5 Zornitza Stark reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Polycystic kidney disease 7, MIM# 620056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.378 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Genetic epilepsy with febrile seizures plus to Genetic epilepsy with febrile seizures plus; Developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related
Mendeliome v1.377 SLC32A1 Zornitza Stark Publications for gene: SLC32A1 were set to 34038384
Mendeliome v1.376 SCNM1 Elena Savva Gene: scnm1 has been classified as Green List (High Evidence).
Mendeliome v1.376 SCNM1 Elena Savva Classified gene: SCNM1 as Green List (high evidence)
Mendeliome v1.376 SCNM1 Elena Savva Gene: scnm1 has been classified as Green List (High Evidence).
Mendeliome v1.375 SCNM1 Elena Savva gene: SCNM1 was added
gene: SCNM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCNM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCNM1 were set to PMID: 36084634
Phenotypes for gene: SCNM1 were set to Ciliopathy, SCNM1-related, MONDO:0005308
Review for gene: SCNM1 was set to GREEN
Added comment: Iturrate (2022): three unrelated families (4 affected) w/ OFD, polydactyly, syndactyly and brachydactyly. All had biallelic variants (fs, missense, AluYc1 sequence insertion) and were consanguinous
- the missense variant was shown to have a splice outcome
Sources: Literature
Mendeliome v1.374 DEPDC5 Dean Phelan reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36067010, 32848577; Phenotypes: Neurodevelopmental disorder, DEPDC5-related, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.374 LETM1 Zornitza Stark Marked gene: LETM1 as ready
Mendeliome v1.374 LETM1 Zornitza Stark Gene: letm1 has been classified as Green List (High Evidence).
Mendeliome v1.374 LETM1 Zornitza Stark reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.374 LETM1 Zornitza Stark Classified gene: LETM1 as Green List (high evidence)
Mendeliome v1.374 LETM1 Zornitza Stark Gene: letm1 has been classified as Green List (High Evidence).
Mendeliome v1.373 DACT1 Zornitza Stark Classified gene: DACT1 as Amber List (moderate evidence)
Mendeliome v1.373 DACT1 Zornitza Stark Gene: dact1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.372 LETM1 Ee Ming Wong gene: LETM1 was added
gene: LETM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214
Phenotypes for gene: LETM1 were set to Mitochondrial disease MONDO#0044970, LETM1-related
gene: LETM1 was marked as current diagnostic
Added comment: -18 affected individuals from 11 unrelated families harbouring ultra-rare bi-allelic missense and loss-of-function LETM1 variants
-Most of the affected individuals (14/18, 78%) had an infantile-onset disease manifestation,
and 4/18 (22%) presented first symptoms between the ages of 1.5 and 2 years
-Variant types included missense, frameshift, stop loss, in-frame deletion and splice defect
-From biochemical and morphological studies, bi-allelic LETM1 variants are associated with defective mitochondrial K efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components
Sources: Literature
Mendeliome v1.372 GABRG1 Seb Lunke Gene: gabrg1 has been classified as Red List (Low Evidence).
Mendeliome v1.372 GABBR1 Zornitza Stark Gene: gabbr1 has been classified as Green List (High Evidence).
Mendeliome v1.372 GABBR1 Zornitza Stark Classified gene: GABBR1 as Green List (high evidence)
Mendeliome v1.372 GABBR1 Zornitza Stark Gene: gabbr1 has been classified as Green List (High Evidence).
Mendeliome v1.371 GABBR1 Zornitza Stark gene: GABBR1 was added
gene: GABBR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR1 were set to 36103875
Phenotypes for gene: GABBR1 were set to Neurodevelopmental disorder, GABBR1-related, MONDO:0700092
Review for gene: GABBR1 was set to GREEN
Added comment: Four individuals with de novo variants in this gene and varying severity of DD/ID, seizures and hypotonia.
Sources: Literature
Mendeliome v1.371 GABRG1 Seb Lunke Classified gene: GABRG1 as Red List (low evidence)
Mendeliome v1.371 GABRG1 Seb Lunke Gene: gabrg1 has been classified as Red List (Low Evidence).
Mendeliome v1.370 DUT Seb Lunke Marked gene: DUT as ready
Mendeliome v1.370 DUT Seb Lunke Gene: dut has been classified as Green List (High Evidence).
Mendeliome v1.370 DUT Seb Lunke Classified gene: DUT as Green List (high evidence)
Mendeliome v1.370 DUT Seb Lunke Gene: dut has been classified as Green List (High Evidence).
Mendeliome v1.369 DUT Daniel Flanagan gene: DUT was added
gene: DUT was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUT were set to 28073829; 35611808
Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome (MIM#620044)
Review for gene: DUT was set to GREEN
Added comment: Homozygous missense (p.(Tyr142Cys)) identified in eight affected individuals from four unrelated consanguineous families (French, Egyptian, two Libyan) with diabetes and bone marrow failure. DUT silencing in human and rat pancreatic b-cells results in apoptosis via the intrinsic cell death pathway.

p.(Tyr142Cys) has 11 heterozygotes and no homozygotes in gnomAD.
Sources: Expert list
Mendeliome v1.369 DACT1 Paul De Fazio reviewed gene: DACT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36066768; Phenotypes: Townes-Brocks syndrome 2 MONDO:0054582; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v1.369 CENPP Seb Lunke Gene: cenpp has been classified as Red List (Low Evidence).
Mendeliome v1.369 CENPP Seb Lunke changed review comment from: Sources: Literature; to: Single family with dominant SNHL segregated through 5 family members. Truncating variant in NM_001012267.3(CENPP):c.849T>A (p.Cys283Ter). Note: misannotated as nonsense variant in paper.
Sources: Literature
Mendeliome v1.369 CENPP Seb Lunke gene: CENPP was added
gene: CENPP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CENPP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CENPP were set to 36071244
Phenotypes for gene: CENPP were set to autosomal dominant nonsyndromic hearing loss; MONDO:0019587
Review for gene: CENPP was set to RED
Added comment: Sources: Literature
Mendeliome v1.368 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Red List (Low Evidence).
Mendeliome v1.368 GABRG1 Anna Ritchie gene: GABRG1 was added
gene: GABRG1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GABRG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRG1 were set to PMID: 36121006
Phenotypes for gene: GABRG1 were set to Developmental and epileptic encephalopathy MONDO:0100062
Added comment: 2-year-old patient with epileptic encephalopathy, hypotonia, and global developmental delays. Clinical trio exome sequencing showed a novel, de novo missense variant in the GABRG1 gene.
Sources: Literature
Mendeliome v1.368 SLC32A1 Lucy Spencer reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36073542; Phenotypes: developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.368 SLC13A1 Zornitza Stark Classified gene: SLC13A1 as Red List (low evidence)
Mendeliome v1.368 SLC13A1 Zornitza Stark Gene: slc13a1 has been classified as Red List (Low Evidence).
Mendeliome v1.367 MED11 Ain Roesley Gene: med11 has been classified as Green List (High Evidence).
Mendeliome v1.367 MED11 Ain Roesley Classified gene: MED11 as Green List (high evidence)
Mendeliome v1.367 MED11 Ain Roesley Gene: med11 has been classified as Green List (High Evidence).
Mendeliome v1.366 LAMA5 Belinda Chong reviewed gene: LAMA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 29534211, 16790509, 29764427, 30808327, 24130771, 35419533; Phenotypes: Nephrotic syndrome, type 26 620049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.366 MED11 Ain Roesley gene: MED11 was added
gene: MED11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to neurodevelopmental disorder MONDO#0700092, MED11-related
Review for gene: MED11 was set to GREEN
gene: MED11 was marked as current diagnostic
Added comment: 7 affected from 5 families (3x consang) with the same recurrent variant of p.(Arg109*).

Protein truncating, NOT NMD as proven by RT-PCR and western blot. Zebrafish knockout model recapitulates key clinical phenotypes

NO evidence of founder effect from haplotype analysis

7/7 cerebral dysgyria, cortical atrophy
5/7 limb contracture
4/7 epilepsy
3/7 families with IUGR
3/7 GDD
3/7 hearing loss
3/7 undescended testis
2/7 nystagmus
1/7 congenital cataract
Sources: Literature
Mendeliome v1.365 ATP6V0C Naomi Baker reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:36074901; Phenotypes: neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.365 ATP6V0C Alison Yeung Classified gene: ATP6V0C as Green List (high evidence)
Mendeliome v1.365 ATP6V0C Alison Yeung Gene: atp6v0c has been classified as Green List (High Evidence).
Mendeliome v1.364 ATP6V0C Alison Yeung reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: 36074901; Phenotypes: neurodevelopmental disorder (MONDO:0700092), ATP6V0C-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.364 SLC13A1 Lucy Spencer gene: SLC13A1 was added
gene: SLC13A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC13A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A1 were set to 36175384
Phenotypes for gene: SLC13A1 were set to sulfation-related bone disorder MONDO:0019688, SLC13A1-related
Review for gene: SLC13A1 was set to RED
Added comment: PMID: 36175384- 1 patient with a homozygous nonsense variant in SLC13A1. Patient has enlargements of the joints, and spondylo-epi-metaphyseal radiological abnormalities in early childhood, which improved with age. Also autistic features and hyposulfatemia and hypersulfaturia, and reduced serum cholesterol sulfate. However the variant in this individual (Arg12Ter) has 569 hets and 1 hom in gnomad.

Also this patient was homozygous for CFTR Ala455Gly which is a known pathogenic variant associated with a less severe CF phenotype.
Sources: Literature
Mendeliome v1.364 LAMA5 Zornitza Stark Classified gene: LAMA5 as Green List (high evidence)
Mendeliome v1.364 LAMA5 Zornitza Stark Gene: lama5 has been classified as Green List (High Evidence).
Mendeliome v1.363 LAMA5 Zornitza Stark reviewed gene: LAMA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 35419533; Phenotypes: Nephrotic syndrome, type 26 620049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.363 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Mendeliome v1.363 NAPB Alison Yeung Classified gene: NAPB as Green List (high evidence)
Mendeliome v1.363 NAPB Alison Yeung Gene: napb has been classified as Green List (High Evidence).
Mendeliome v1.362 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Mendeliome v1.362 FKBP6 Zornitza Stark Classified gene: FKBP6 as Green List (high evidence)
Mendeliome v1.362 FKBP6 Zornitza Stark Gene: fkbp6 has been classified as Green List (High Evidence).
Mendeliome v1.361 MTSS1L Elena Savva Marked gene: MTSS1L as ready
Mendeliome v1.361 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Mendeliome v1.361 SARS Ee Ming Wong edited their review of gene: SARS: Added comment: -Two missense variants within the aminoacylation domain identified in 16 affected individuals from 3 distinct CMT families
-Mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation; Changed rating: GREEN; Changed publications: 36088542; Changed phenotypes: Genetic peripheral neuropathy MONDO#0020127, SARS1-related
Mendeliome v1.361 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Mendeliome v1.361 FOSL2 Zornitza Stark Classified gene: FOSL2 as Green List (high evidence)
Mendeliome v1.361 FOSL2 Zornitza Stark Gene: fosl2 has been classified as Green List (High Evidence).
Mendeliome v1.360 MTSS1L Elena Savva Classified gene: MTSS1L as Green List (high evidence)
Mendeliome v1.360 MTSS1L Elena Savva Gene: mtss1l has been classified as Green List (High Evidence).
Mendeliome v1.359 MTSS1L Elena Savva gene: MTSS1L was added
gene: MTSS1L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MTSS1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MTSS1L were set to PMID: 36067766
Phenotypes for gene: MTSS1L were set to Intellectual disability, MTSS2-related (MONDO#0001071)
Review for gene: MTSS1L was set to GREEN
Added comment: Alt gene name: MTSS2

Huang (2022): recurring de novo missense variant (p.R671W) causing syndromic intellectual disability in 5 unrelated individuals.
- Individuals present with GDD, mild ID (5/5), nystagmus (3/5), optic atrophy (1/5), ptosis (2/5), sensorineural hearing loss (2/4), microcephaly or relative microcephaly (5/5), and shared mild facial dysmorphisms.
- Overexpression supports a DN mechanism
Sources: Literature
Mendeliome v1.358 DAW1 Alison Yeung Gene: daw1 has been classified as Green List (High Evidence).
Mendeliome v1.358 DAW1 Alison Yeung Classified gene: DAW1 as Green List (high evidence)
Mendeliome v1.358 DAW1 Alison Yeung Gene: daw1 has been classified as Green List (High Evidence).
Mendeliome v1.357 DAW1 Alison Yeung gene: DAW1 was added
gene: DAW1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAW1 were set to 36074124
Phenotypes for gene: DAW1 were set to Primary ciliary dyskinesia, MONDO:0016575; Visceral heterotaxy, MONDO:0018677
Review for gene: DAW1 was set to GREEN
Added comment: Biallelic variants identified in two unrelated families. Zebrafish model recapitulates PCD and heterotaxy phenotype
Sources: Literature
Mendeliome v1.356 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Mendeliome v1.356 RABGAP1 Zornitza Stark Classified gene: RABGAP1 as Green List (high evidence)
Mendeliome v1.356 RABGAP1 Zornitza Stark Gene: rabgap1 has been classified as Green List (High Evidence).
Mendeliome v1.355 RABGAP1 Zornitza Stark gene: RABGAP1 was added
gene: RABGAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RABGAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RABGAP1 were set to 36083289
Phenotypes for gene: RABGAP1 were set to Neurodevelopmental disorder, RABGAP1-related,MONDO:0700092
Review for gene: RABGAP1 was set to GREEN
Added comment: 5 individuals from three families reported with ID, microcephaly, SNHL and seizures. Mouse model recapitulated the phenotype.
Sources: Literature
Mendeliome v1.354 NAPB Paul De Fazio gene: NAPB was added
gene: NAPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAPB were set to 26235277; 28097321; 33189936
Phenotypes for gene: NAPB were set to Developmental and epileptic encephalopathy 107 MIM#620033
Review for gene: NAPB was set to GREEN
gene: NAPB was marked as current diagnostic
Added comment: PMID 26235277: homozygous nonsense variant identified in a 6 year old girl by trio WES with early-onset epileptic encephalopathy characterised by multifocal seizures and profound GDD

PMID 28097321: exome sequencing in 152 consanguineous families with at least one member affected with ID. Homozygous nonsense variant identified in a patient with profound ID, seizures, feeding difficulties in infancy, muscularhypotonia, microcephaly, and impaired vision

PMID 33189936: homozygous canonical splice variant identified by trio exome sequencing in two siblings with seizures, intellectual disability and global developmental delay, microcephaly (<-3SD), and muscular hypotonia.
Sources: Literature
Mendeliome v1.354 FKBP6 Dean Phelan gene: FKBP6 was added
gene: FKBP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FKBP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP6 were set to PMID: 36150389
Phenotypes for gene: FKBP6 were set to Spermatogenic failure (MONDO:0004983), FKBP6-related
Review for gene: FKBP6 was set to GREEN
Added comment: PMID: 36150389 - large cohort study of men with severe spermatogenic failure (SPGF), identified six individuals with rare bi-allelic loss of function variants in FKBP6. RT-qPCR and immunofluorescence confirmed lack of FKBP6 expression. In mice, Fkbp6 has also been shown to be essential for spermatogenesis.
Sources: Literature
Mendeliome v1.354 GCSH Ain Roesley Phenotypes for gene: GCSH were changed from Glycine encephalopathy, MIM# 605899 to Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related
Mendeliome v1.353 GCSH Ain Roesley Publications for gene: GCSH were set to 1671321
Mendeliome v1.352 GCSH Ain Roesley edited their review of gene: GCSH: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.352 GCSH Ain Roesley edited their review of gene: GCSH: Changed phenotypes: Glycine encephalopathy MIM#605899, neurodevelopmental disorder MONDO#0700092, GCHS-related
Mendeliome v1.352 GCSH Ain Roesley Classified gene: GCSH as Green List (high evidence)
Mendeliome v1.352 GCSH Ain Roesley Gene: gcsh has been classified as Green List (High Evidence).
Mendeliome v1.351 GCSH Ain Roesley reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: glycine encephalopathy MONDO#0011612, GCSH-related, neurodevelopmental disorder MONDO#0700092, GCHS-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.351 NSD2 Zornitza Stark Publications for gene: NSD2 were set to 30345613; 31171569
Mendeliome v1.350 NSD2 Zornitza Stark edited their review of gene: NSD2: Changed publications: 36189577
Mendeliome v1.350 NSD2 Zornitza Stark Phenotypes for gene: NSD2 were changed from Rauch-Steindl syndrome, MIM# 619695; Microcephaly; intellectual disability to Rauch-Steindl syndrome, MIM# 619695; Microcephaly; intellectual disability; Neurodevelopmental disorder, NSD2-associated, GoF, MONDO:0700092
Mendeliome v1.349 NSD2 Zornitza Stark Publications for gene: NSD2 were set to 30345613; 31171569
Mendeliome v1.348 NSD2 Zornitza Stark edited their review of gene: NSD2: Added comment: PMID 36189577: two individuals reported with a GoF variant, p.Glu1099Lys, and a distinct phenotype: intellectual disability, coarse/ square facial gestalt, abnormalities of the hands, and organomegaly.; Changed phenotypes: Rauch-Steindl syndrome, MIM# 619695, Microcephaly, intellectual disability, Neurodevelopmental disorder, NSD2-associated, GoF, MONDO:0700092
Mendeliome v1.348 FOSL2 Krithika Murali gene: FOSL2 was added
gene: FOSL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOSL2 were set to 36197437
Phenotypes for gene: FOSL2 were set to Neurodevelopmental disorder, MONDO:0700092, FOSL2-related
Review for gene: FOSL2 was set to GREEN
Added comment: PMID 36197437 Cospain et al 2022 report 11 individuals from 10 families with heterozygous PTC variants in exon 4/4 of the FOSL2 gene. All variants were predicted to escape NMD resulting in a truncated protein, with the truncation occurring proximal to the C-terminal domain (supportive functional studies).

In 10/11 families the variant occurred de novo in a single affected proband. In one family with 2 affected siblings, the variant was present in the siblings but absent in the unaffected parent likely due to gonadal mosaicism.

Clinical features included:
- Cutis aplasia congenital of the scalp (10/11)
- Tooth enamel hypoplasia and discolouration (8/9)
- Multiple other ectodermal features also noted e.g. small brittle nails, hypotrichosis/hypertrichosis, lichen sclerosis
- 5 individuals had cataracts (mostly bilateral, congenital/early childhood onset)
- 6/9 IUGR
- 5/9 postnatal growth restriction
- 7/9 developmental delay/ID
- 5/7 ADHD/ASD
- 2/9 seizures
Sources: Literature
Mendeliome v1.348 TRAF3 Zornitza Stark Publications for gene: TRAF3 were set to 20832341
Mendeliome v1.347 TRAF3 Zornitza Stark Classified gene: TRAF3 as Green List (high evidence)
Mendeliome v1.347 TRAF3 Zornitza Stark Gene: traf3 has been classified as Green List (High Evidence).
Mendeliome v1.346 TRAF3 Zornitza Stark changed review comment from: Single individual reported.; to: Single individual reported with HSV-induced encephalopathy.
Mendeliome v1.346 TRAF3 Zornitza Stark edited their review of gene: TRAF3: Added comment: PMID 35960817: Nine individuals from five unrelated families with childhood-onset immune diseases and recurrent infections. All patients had suffered recurrent ear and sinopulmonary infections, including pneumonias from encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenza, resulting in early-onset bronchiectasis in several individuals; Changed rating: GREEN; Changed publications: 20832341, 35960817; Changed phenotypes: Autoinflammatory syndrome, TRAF3-related, MONDO:0019751, hypergammaglobulinemia, lymphadenopathy, splenomegaly, Sjögren’s syndrome, {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, MIM# 614849
Mendeliome v1.346 KCNK3 Krithika Murali reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36195757; Phenotypes: eurodevelopmental disorder, MONDO:0700092, KCNK3-related, developmental delay with sleep apnoea (DDSA), Pulmonary hypertension, primary, 4-MIM#615344; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.346 MYSM1 Zornitza Stark Tag treatable tag was added to gene: MYSM1.
Mendeliome v1.346 MOCS1 Zornitza Stark Tag treatable tag was added to gene: MOCS1.
Mendeliome v1.346 MLYCD Zornitza Stark Tag treatable tag was added to gene: MLYCD.
Mendeliome v1.346 COQ8A Zornitza Stark Tag treatable tag was added to gene: COQ8A.
Mendeliome v1.346 COQ4 Zornitza Stark changed review comment from: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported.; to: Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. At least 9 unrelated families reported.

Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.
Mendeliome v1.346 COQ4 Zornitza Stark Tag treatable tag was added to gene: COQ4.
Mendeliome v1.346 COLQ Zornitza Stark Tag treatable tag was added to gene: COLQ.
Tag clinical trial tag was added to gene: COLQ.
Mendeliome v1.346 CHRNE Zornitza Stark Tag treatable tag was added to gene: CHRNE.
Mendeliome v1.346 CHRND Zornitza Stark Tag treatable tag was added to gene: CHRND.
Mendeliome v1.346 CHRNA1 Zornitza Stark Tag treatable tag was added to gene: CHRNA1.
Mendeliome v1.346 ADAMTS19 Zornitza Stark Phenotypes for gene: ADAMTS19 were changed from Non-syndromic heart valve disease to Cardiac valvular dysplasia 2, MIM# 620067
Mendeliome v1.345 ADAMTS19 Zornitza Stark edited their review of gene: ADAMTS19: Changed phenotypes: Cardiac valvular dysplasia 2, MIM# 620067
Mendeliome v1.345 DOHH Zornitza Stark Phenotypes for gene: DOHH were changed from Neurodevelopmental disorder, DOHH-related (MONDO#0700092) to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066
Mendeliome v1.344 DOHH Zornitza Stark reviewed gene: DOHH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM# 620066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.344 DPH2 Zornitza Stark Phenotypes for gene: DPH2 were changed from Diphthamide-deficiency syndrome to Developmental delay with short stature, dysmorphic facial features, and sparse hair 2, MIM# 620062; Diphthamide-deficiency syndrome
Mendeliome v1.343 DPH2 Zornitza Stark reviewed gene: DPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair 2, MIM# 620062; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.343 CHAT Zornitza Stark Tag treatable tag was added to gene: CHAT.
Mendeliome v1.343 CA5A Zornitza Stark Tag treatable tag was added to gene: CA5A.
Mendeliome v1.343 BTK Zornitza Stark Tag treatable tag was added to gene: BTK.
Mendeliome v1.343 ASL Zornitza Stark Tag treatable tag was added to gene: ASL.
Mendeliome v1.343 ARSB Zornitza Stark Tag clinical trial tag was added to gene: ARSB.
Mendeliome v1.343 ARSB Zornitza Stark Tag treatable tag was added to gene: ARSB.
Mendeliome v1.343 ARG1 Zornitza Stark Tag treatable tag was added to gene: ARG1.
Mendeliome v1.343 AHCY Zornitza Stark Tag treatable tag was added to gene: AHCY.
Mendeliome v1.343 SMN1 Zornitza Stark Tag treatable tag was added to gene: SMN1.
Tag clinical trial tag was added to gene: SMN1.
Mendeliome v1.343 ACADVL Zornitza Stark Tag treatable tag was added to gene: ACADVL.
Mendeliome v1.343 GALE Zornitza Stark Tag treatable tag was added to gene: GALE.
Mendeliome v1.343 GALK1 Zornitza Stark Tag treatable tag was added to gene: GALK1.
Mendeliome v1.343 GALT Zornitza Stark Tag treatable tag was added to gene: GALT.
Mendeliome v1.343 TAT Zornitza Stark Tag treatable tag was added to gene: TAT.
Mendeliome v1.343 PCCB Zornitza Stark Tag treatable tag was added to gene: PCCB.
Mendeliome v1.343 PCCA Zornitza Stark Tag treatable tag was added to gene: PCCA.
Mendeliome v1.343 PTS Zornitza Stark Tag treatable tag was added to gene: PTS.
Mendeliome v1.343 PAH Zornitza Stark Tag treatable tag was added to gene: PAH.
Mendeliome v1.343 ETFB Zornitza Stark Tag treatable tag was added to gene: ETFB.
Mendeliome v1.343 ETFA Zornitza Stark Tag treatable tag was added to gene: ETFA.
Mendeliome v1.343 ETFDH Zornitza Stark Tag treatable tag was added to gene: ETFDH.
Mendeliome v1.343 HADHB Zornitza Stark Tag treatable tag was added to gene: HADHB.
Mendeliome v1.343 HADHA Zornitza Stark Tag treatable tag was added to gene: HADHA.
Mendeliome v1.343 MMAB Zornitza Stark Tag treatable tag was added to gene: MMAB.
Mendeliome v1.343 MMAA Zornitza Stark Tag treatable tag was added to gene: MMAA.
Mendeliome v1.343 MUT Zornitza Stark Tag new gene name tag was added to gene: MUT.
Mendeliome v1.343 MUT Zornitza Stark Tag treatable tag was added to gene: MUT.
Mendeliome v1.343 ACADM Zornitza Stark Tag acadm was removed from gene: ACADM.
Tag treatable tag was added to gene: ACADM.
Mendeliome v1.343 ACADM Zornitza Stark Tag acadm tag was added to gene: ACADM.
Mendeliome v1.343 IVD Zornitza Stark Tag treatable tag was added to gene: IVD.
Mendeliome v1.343 BTD Zornitza Stark Tag treatable tag was added to gene: BTD.
Mendeliome v1.343 HLCS Zornitza Stark Tag treatable tag was added to gene: HLCS.
Mendeliome v1.343 GCDH Zornitza Stark Tag treatable tag was added to gene: GCDH.
Mendeliome v1.343 CBS Zornitza Stark Tag treatable tag was added to gene: CBS.
Mendeliome v1.343 MMADHC Zornitza Stark Tag treatable tag was added to gene: MMADHC.
Mendeliome v1.343 MMACHC Zornitza Stark Tag treatable tag was added to gene: MMACHC.
Mendeliome v1.343 SLC25A20 Zornitza Stark Tag treatable tag was added to gene: SLC25A20.
Mendeliome v1.343 SLC22A5 Zornitza Stark Tag treatable tag was added to gene: SLC22A5.
Mendeliome v1.343 MC2R Zornitza Stark Tag treatable tag was added to gene: MC2R.
Mendeliome v1.343 MAN2B1 Zornitza Stark Tag treatable tag was added to gene: MAN2B1.
Mendeliome v1.343 LYST Zornitza Stark Tag treatable tag was added to gene: LYST.
Mendeliome v1.343 LMBRD1 Zornitza Stark Tag treatable tag was added to gene: LMBRD1.
Mendeliome v1.343 LIPA Zornitza Stark Tag treatable tag was added to gene: LIPA.
Mendeliome v1.343 LIG4 Zornitza Stark Tag treatable tag was added to gene: LIG4.
Mendeliome v1.343 LHX4 Zornitza Stark Tag treatable tag was added to gene: LHX4.
Mendeliome v1.343 LHX3 Zornitza Stark Tag treatable tag was added to gene: LHX3.
Mendeliome v1.343 LEPR Zornitza Stark Tag treatable tag was added to gene: LEPR.
Tag clinical trial tag was added to gene: LEPR.
Mendeliome v1.343 CPT2 Zornitza Stark Tag treatable tag was added to gene: CPT2.
Mendeliome v1.343 CPT1A Zornitza Stark Tag treatable tag was added to gene: CPT1A.
Mendeliome v1.343 BCKDHB Zornitza Stark Tag treatable tag was added to gene: BCKDHB.
Mendeliome v1.343 BCKDHA Zornitza Stark Tag treatable tag was added to gene: BCKDHA.
Mendeliome v1.343 DBT Zornitza Stark Tag treatable tag was added to gene: DBT.
Mendeliome v1.343 HMGCL Zornitza Stark Tag treatable tag was added to gene: HMGCL.
Mendeliome v1.343 ACAT1 Zornitza Stark Tag treatable tag was added to gene: ACAT1.
Mendeliome v1.343 ASS1 Zornitza Stark Tag treatable tag was added to gene: ASS1.
Mendeliome v1.343 BLNK Zornitza Stark Tag treatable tag was added to gene: BLNK.
Mendeliome v1.343 TYMS Zornitza Stark Tag digenic tag was added to gene: TYMS.
Mendeliome v1.343 TYMS Zornitza Stark Phenotypes for gene: TYMS were changed from Dyskeratosis congenita MONDO:0015780 to Dyskeratosis congenita, digenic, MIM#620040
Mendeliome v1.342 TYMS Zornitza Stark edited their review of gene: TYMS: Changed phenotypes: Dyskeratosis congenita, digenic, MIM#620040
Mendeliome v1.342 ACVR1 Zornitza Stark Tag clinical trial tag was added to gene: ACVR1.
Mendeliome v1.342 ACVR1 Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Clinical trial with palovarotene

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.
Mendeliome v1.342 ALDOB Zornitza Stark Tag treatable tag was added to gene: ALDOB.
Mendeliome v1.342 ALDOB Zornitza Stark reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fructose intolerance, hereditary, MIM# 229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.342 ATP7A Zornitza Stark changed review comment from: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.; to: ATP7A-related copper transport disorders are classically separated in three pathologies according to their severity, all inherited in an X-linked recessive manner: Menkes disease (MD, OMIM #309400) which represent more than 90% of cases; occipital Horn Syndrome (OHS, OMIM #304150) and ATP7A-related distal motor neuropathy also named X-linked distal spinal muscular atrophy-3 (SMAX3, OMIM #300489). Although there is no clear cut correlation between Cu and ceruloplasmin levels in ATP7A related disorders, these three entities probably represent a continuum partly depending on residual functional ATP7A protein.

Treatment for Menkes disease: subcutaneous injections of copper histidine or copper chloride

ClinGen has assessed as moderate evidence for actionability.

Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms.
Mendeliome v1.342 ATP7A Zornitza Stark Tag treatable tag was added to gene: ATP7A.
Mendeliome v1.342 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580
Mendeliome v1.341 PDCD6IP Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Neurodevelopmental disorder MONDO:0700092; Microcephaly; intellectual disability to Microcephaly 29, primary, autosomal recessive, MIM# 620047; Microcephaly; intellectual disability
Mendeliome v1.340 PDCD6IP Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive, MIM# 620047, Microcephaly, intellectual disability
Mendeliome v1.340 PDCD6IP Zornitza Stark edited their review of gene: PDCD6IP: Changed phenotypes: Microcephaly 29, primary, autosomal recessive , MIM# 620047, Microcephaly, intellectual disability
Mendeliome v1.340 DPP9 Zornitza Stark Gene: dpp9 has been classified as Green List (High Evidence).
Mendeliome v1.340 DPP9 Zornitza Stark Classified gene: DPP9 as Green List (high evidence)
Mendeliome v1.340 DPP9 Zornitza Stark Gene: dpp9 has been classified as Green List (High Evidence).
Mendeliome v1.339 DPP9 Zornitza Stark gene: DPP9 was added
gene: DPP9 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DPP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPP9 were set to 36112693
Phenotypes for gene: DPP9 were set to Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Review for gene: DPP9 was set to GREEN
Added comment: Three unrelated families with Hatipoğlu syndrome with biochemical and cellular assays, mouse and zebrafish models. Immunological features of recurrent fevers, repeated infections, herpes susceptibility, cytopenias.
Sources: Expert Review
Mendeliome v1.338 ATP6V1B1 Zornitza Stark Tag treatable tag was added to gene: ATP6V1B1.
Mendeliome v1.338 ATP6V0A4 Zornitza Stark Tag treatable tag was added to gene: ATP6V0A4.
Mendeliome v1.338 ARSA Zornitza Stark Tag treatable tag was added to gene: ARSA.
Tag clinical trial tag was added to gene: ARSA.
Mendeliome v1.338 ARPC1B Zornitza Stark changed review comment from: Three families with functional data.; to: Three families with functional data.

Treatment: BMT.
Mendeliome v1.338 ARPC1B Zornitza Stark Tag treatable tag was added to gene: ARPC1B.
Mendeliome v1.338 AVPR2 Zornitza Stark Tag clinical trial tag was added to gene: AVPR2.
Mendeliome v1.338 AVPR2 Zornitza Stark reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes insipidus, nephrogenic 304800, Nephrogenic syndrome of inappropriate antidiuresis 300539; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.338 AVPR2 Zornitza Stark Tag treatable tag was added to gene: AVPR2.
Mendeliome v1.338 AVP Zornitza Stark reviewed gene: AVP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes insipidus, neurohypophyseal MIM#125700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.338 AVP Zornitza Stark Tag treatable tag was added to gene: AVP.
Tag clinical trial tag was added to gene: AVP.
Mendeliome v1.338 AQP2 Zornitza Stark Tag treatable tag was added to gene: AQP2.
Tag clinical trial tag was added to gene: AQP2.
Mendeliome v1.338 AQP2 Zornitza Stark changed review comment from: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants.; to: Dominant disease is caused by variants exerting a dominant negative effect, whereas recessive disease is caused by bi-allelic loss of function variants.

Onset in infancy. Causes severe dehydration, can be life-threatening.

Treatment: hydration, low-salt, low-protein diet, thiazide diuretics, amiloride, indomethacin.

Clinical trials.
Mendeliome v1.338 APRT Zornitza Stark changed review comment from: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic.; to: APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic.

Treatable: allopurinol or febuxostat, low purine diet.
Mendeliome v1.338 APRT Zornitza Stark Tag treatable tag was added to gene: APRT.
Mendeliome v1.338 APRT Zornitza Stark reviewed gene: APRT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenine phosphoribosyltransferase deficiency MIM#614723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.338 AP3B1 Zornitza Stark Tag treatable tag was added to gene: AP3B1.
Tag clinical trial tag was added to gene: AP3B1.
Mendeliome v1.338 ALPL Zornitza Stark Tag treatable tag was added to gene: ALPL.
Mendeliome v1.338 ANO1 Zornitza Stark Phenotypes for gene: ANO1 were changed from Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features to Intestinal dysmotility syndrome, MIM# 620045; Impaired intestinal peristalsis; haemorrhagic diarrhoea; dysmorphic features
Mendeliome v1.337 ANO1 Zornitza Stark reviewed gene: ANO1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intestinal dysmotility syndrome, MIM# 620045; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.337 ADAMTS13 Zornitza Stark Tag treatable tag was added to gene: ADAMTS13.
Mendeliome v1.337 AK2 Zornitza Stark Tag treatable tag was added to gene: AK2.
Mendeliome v1.337 AGRN Zornitza Stark Tag treatable tag was added to gene: AGRN.
Tag clinical trial tag was added to gene: AGRN.
Mendeliome v1.337 ABCG5 Zornitza Stark Tag treatable tag was added to gene: ABCG5.
Tag clinical trial tag was added to gene: ABCG5.
Mendeliome v1.337 ABCC6 Zornitza Stark Phenotypes for gene: ABCC6 were changed from Pseudoxanthoma elasticum, MIM# 264800; Pseudoxanthoma elasticum, forme fruste, MIM#177850 to Arterial calcification, generalized, of infancy, 2, MIM# 614473; Pseudoxanthoma elasticum, MIM# 264800; Pseudoxanthoma elasticum, forme fruste, MIM#177850
Mendeliome v1.336 ABCC6 Zornitza Stark Publications for gene: ABCC6 were set to 11536079; 28102862
Mendeliome v1.335 ABCC6 Zornitza Stark Tag treatable tag was added to gene: ABCC6.
Mendeliome v1.335 ABCC6 Zornitza Stark edited their review of gene: ABCC6: Added comment: GACI is a treatable disorder.; Changed rating: GREEN; Changed publications: 33005041, 34355424; Changed phenotypes: Arterial calcification, generalized, of infancy, 2, MIM# 614473; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.335 ALDH7A1 Zornitza Stark Tag treatable tag was added to gene: ALDH7A1.
Mendeliome v1.335 AKR1D1 Zornitza Stark Tag treatable tag was added to gene: AKR1D1.
Mendeliome v1.335 AGXT Zornitza Stark Tag treatable tag was added to gene: AGXT.
Tag clinical trial tag was added to gene: AGXT.
Mendeliome v1.335 NDNF Elena Savva Phenotypes for gene: NDNF were changed from Congenital hypogonadotropic hypogonadism (CHH) to Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Mendeliome v1.334 NDNF Elena Savva Classified gene: NDNF as Amber List (moderate evidence)
Mendeliome v1.334 NDNF Elena Savva Gene: ndnf has been classified as Amber List (Moderate Evidence).
Mendeliome v1.333 NDNF Elena Savva reviewed gene: NDNF: Rating: AMBER; Mode of pathogenicity: None; Publications: 31883645; Phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.333 GIF Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is CBLIF.
Mendeliome v1.333 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Mendeliome v1.333 GIF Zornitza Stark Tag new gene name tag was added to gene: GIF.
Mendeliome v1.333 PTPA Zornitza Stark Marked gene: PTPA as ready
Mendeliome v1.333 PTPA Zornitza Stark Gene: ptpa has been classified as Amber List (Moderate Evidence).
Mendeliome v1.333 PTPA Zornitza Stark Classified gene: PTPA as Amber List (moderate evidence)
Mendeliome v1.333 PTPA Zornitza Stark Gene: ptpa has been classified as Amber List (Moderate Evidence).
Mendeliome v1.332 PTPA Zornitza Stark gene: PTPA was added
gene: PTPA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPA were set to 36073231
Phenotypes for gene: PTPA were set to Intellectual disability, MONDO: 36073231, PTPA-related
Review for gene: PTPA was set to AMBER
Added comment: Biallelic PTPA pathogenic variants lead to a form of ID with later-onset parkinsonism based on 4 individuals from 2 families in the literature. Affected individuals were homozygous for missense variants demonstrated to result to reduced mRNA and protein levels as well as PP2A complex activation. Drosophila studies support an age-dependent locomotor dysfunction. Variants in other PP2A-complex-related genes also lead to NDDs. Summary provided below.

There is currently no associated phenotype in OMIM, G2P, PanelApp UK or SysID.

Consider inclusion in relevant panels (ID, Parkinsonism/movement disorders, etc) with amber rating pending further reports.

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Fevga, Tesson et al (2022 - PMID: 36073231) describe the features of 4 individuals, from 2 unrelated families, with biallelic pathogenic PTPA variants.

These presented with normal or delayed early milestones, learning disability and ID (mild to moderate) followed by progressive signs of parkinsonism (at the age of 11 yrs in 2 sibs, 15 yrs in another individual). Motor symptoms were responsive to levodopa and later to deep brain stimulation.

Linkage analysis in one consanguineous family followed by exome revealed homozygosity for a missense PTPA variant (NM_178001:c.893T>G/p.Met298Arg). Exome sequencing in affected subjects from the 2nd family revealed homozygosity for a further missense variant (c.512C>A/p.Ala171Asp). There were no other candidate variants for the phenotype following parental / segregation studies.

Role of the gene:
As the authors discuss, PTPA (or PPP2R4) is ubiquitously expressed in all tissues incl. brain and encodes a phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A). PP2A in turn, is the major Ser/Thr phosphatase in brain targeting a large number of proteins involved in diverse functions. Activation of PP2A is dependent on its methylation, which is negatively regulated by the PP2A-specific methylesterase (PME-1). By binding to PME-1, PTPA counteracts the negative influence of the former on PP2A. Pathogenic variants in genes encoding subunits/regulators of the PP2A complex (e.g. PPP2R1A or PPP2CA) are associated with neurodevelopmental disorders.

Variant studies:
Upon overexpression of wt and both variants in a HEK-293 cell line the authors demonstrated that both variants resulted in significantly reduced mRNA and protein levels (which for Ala171Asp were attributed to increased proteasomal degradation). Both variants were shown to result in impaired PP2A complex activation compared to wt.

Drosophila / animal models:
Pan-neuronal RNAi-mediated knockdown of ptpa in Drosophila resulted in an age-dependent locomotor dysfunction, reversible with L-DOPA treatment.
Previous studies in mice suggest cognitive/electrophysiological impairments upon downregulation of PP2A activity in transgenic mice.
Sources: Literature
Mendeliome v1.331 PKHD1 Zornitza Stark Phenotypes for gene: PKHD1 were changed from Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200 to Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200; Nephrocalcinosis, MONDO:0001567, PKHD1-related
Mendeliome v1.330 PKHD1 Zornitza Stark Publications for gene: PKHD1 were set to
Mendeliome v1.329 PKHD1 Zornitza Stark Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.328 PKHD1 Zornitza Stark edited their review of gene: PKHD1: Added comment: Notę heterozygous carriers reported to have liver cysts and nephrocalcinosis, gene-disease association considered MODERATE by ClinGen.; Changed publications: 28375157, 21945273; Changed phenotypes: Polycystic kidney disease 4, with or without hepatic disease, MIM# 263200, Nephrocalcinosis, MONDO:0001567, PKHD1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.328 PPP2R5C Zornitza Stark Phenotypes for gene: PPP2R5C were changed from macrocephaly; intellectual disability to Neurodevelopmental disorder, PPP2R5C-related (MONDO:070092); macrocephaly; intellectual disability
Mendeliome v1.327 PPP2R5C Zornitza Stark Publications for gene: PPP2R5C were set to
Mendeliome v1.326 PPP2R5C Zornitza Stark Classified gene: PPP2R5C as Green List (high evidence)
Mendeliome v1.326 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Green List (High Evidence).
Mendeliome v1.325 PPP2R5C Teresa Zhao changed review comment from: - ClinVar: two de novo missense variants (p.E177K and p.H188R), one has been reported for intellectual disability

- PMID 25972378: inframe del (T157del) found in a de novo individual with ID, facial asymmetry, conductive HL, overgrowth

- VCGS proband: additional de novo missense variant (p.K299E) found in one individual with syndromic intellectual disability; to: - ClinVar: two de novo missense variants (p.E177K and p.H188R), one has been reported for intellectual disability

- PMID 25972378: inframe del (T157del) found in a de novo individual with ID, facial asymmetry, conductive HL, overgrowth

- VCGS proband: additional de novo missense variant (p.K299E) found in one individual with syndromic intellectual disability
Mendeliome v1.325 PPP2R5C Teresa Zhao reviewed gene: PPP2R5C: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25972378; Phenotypes: Neurodevelopmental disorder, PPP2R5C-related (MONDO:070092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.325 MYH8 Ain Roesley reviewed gene: MYH8: Rating: RED; Mode of pathogenicity: None; Publications: 15590965, 17041932, 15282353; Phenotypes: Carney complex variant MIM#60883; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v1.325 NODAL Zornitza Stark Publications for gene: NODAL were set to 9354794; 19064609
Mendeliome v1.324 NODAL Zornitza Stark Classified gene: NODAL as Amber List (moderate evidence)
Mendeliome v1.324 NODAL Zornitza Stark Gene: nodal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.323 NODAL Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad.

The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED.

A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance.

Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987
Mendeliome v1.323 JAG1 Bryony Thompson reviewed gene: JAG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35819173, 30071989, 14993126, 18570795; Phenotypes: thoracic aortic aneurysm MONDO:0005396; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.323 OOEP Bryony Thompson Phenotypes for gene: OOEP were changed from Multi locus imprinting disturbance in offspring to Multi locus imprinting disturbance in offspring; female infertility due to oocyte meiotic arrest MONDO:0044626
Mendeliome v1.322 OOEP Bryony Thompson Publications for gene: OOEP were set to 29574422
Mendeliome v1.321 OOEP Bryony Thompson Classified gene: OOEP as Amber List (moderate evidence)
Mendeliome v1.321 OOEP Bryony Thompson Gene: ooep has been classified as Amber List (Moderate Evidence).
Mendeliome v1.320 OOEP Bryony Thompson reviewed gene: OOEP: Rating: AMBER; Mode of pathogenicity: None; Publications: 35946397, 18804437; Phenotypes: female infertility due to oocyte meiotic arrest MONDO:0044626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.320 UFSP2 Zornitza Stark Phenotypes for gene: UFSP2 were changed from Neurodevelopmental disorder; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974 to Developmental and epileptic encephalopathy 106, MIM# 620028; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v1.319 UFSP2 Zornitza Stark edited their review of gene: UFSP2: Changed phenotypes: Developmental and epileptic encephalopathy 106, MIM# 620028, Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v1.319 TRAPPC10 Zornitza Stark Phenotypes for gene: TRAPPC10 were changed from neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027
Mendeliome v1.318 TRAPPC10 Zornitza Stark reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.318 UBAP2L Zornitza Stark changed review comment from: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature; to: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in 11 individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature
Mendeliome v1.318 UBAP2L Zornitza Stark Gene: ubap2l has been classified as Green List (High Evidence).
Mendeliome v1.318 UBAP2L Zornitza Stark Classified gene: UBAP2L as Green List (high evidence)
Mendeliome v1.318 UBAP2L Zornitza Stark Gene: ubap2l has been classified as Green List (High Evidence).
Mendeliome v1.317 UBAP2L Zornitza Stark gene: UBAP2L was added
gene: UBAP2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBAP2L were set to 35977029
Phenotypes for gene: UBAP2L were set to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related
Review for gene: UBAP2L was set to GREEN
Added comment: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1).
Sources: Literature
Mendeliome v1.316 ALDH1A2 Zornitza Stark Phenotypes for gene: ALDH1A2 were changed from congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025
Mendeliome v1.315 ALDH1A2 Zornitza Stark reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.315 CHKA Zornitza Stark Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023
Mendeliome v1.314 CHKA Zornitza Stark reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.314 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Red List (Low Evidence).
Mendeliome v1.314 SLC31A1 Zornitza Stark Classified gene: SLC31A1 as Red List (low evidence)
Mendeliome v1.314 SLC31A1 Zornitza Stark Gene: slc31a1 has been classified as Red List (Low Evidence).
Mendeliome v1.313 PPFIBP1 Zornitza Stark Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, MIM# 620024
Mendeliome v1.312 PPFIBP1 Zornitza Stark edited their review of gene: PPFIBP1: Changed publications: 35830857
Mendeliome v1.312 PPFIBP1 Zornitza Stark edited their review of gene: PPFIBP1: Changed phenotypes: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, MIM# 620024
Mendeliome v1.312 PDZD8 Zornitza Stark Gene: pdzd8 has been classified as Green List (High Evidence).
Mendeliome v1.312 PDZD8 Zornitza Stark Classified gene: PDZD8 as Green List (high evidence)
Mendeliome v1.312 PDZD8 Zornitza Stark Gene: pdzd8 has been classified as Green List (High Evidence).
Mendeliome v1.311 PDZD8 Zornitza Stark gene: PDZD8 was added
gene: PDZD8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDZD8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDZD8 were set to 35227461
Phenotypes for gene: PDZD8 were set to Intellectual developmental disorder with autism and dysmorphic facies, MIM# 620021
Review for gene: PDZD8 was set to GREEN
Added comment: Four individuals from two unrelated families, Drosophila and mouse models support gene-disease association.
Sources: Literature
Mendeliome v1.310 SLC31A1 Daniel Flanagan gene: SLC31A1 was added
gene: SLC31A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to PMID: 35913762
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092)
Review for gene: SLC31A1 was set to RED
Added comment: SLC31A1 is also referred to as CTR1.
Monozygotic twins with hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. Homozygous for a novel missense variant (p.(Arg95His)) in copper transporter CTR1, both parents heterozygous. A mouse knock-out model of CTR1 deficiency resulted in prenatal lethality.
Sources: Expert list
Mendeliome v1.310 HNRNPH1 Zornitza Stark Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability to HNRNPH1‐related syndromic intellectual disability; early onset high myopia, MONDO:0001384
Mendeliome v1.309 HNRNPH1 Zornitza Stark Publications for gene: HNRNPH1 were set to 32335897; 29938792
Mendeliome v1.308 TMEM163 Zornitza Stark Marked gene: TMEM163 as ready
Mendeliome v1.308 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.308 TMEM163 Zornitza Stark Phenotypes for gene: TMEM163 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy, MONDO:0019046
Mendeliome v1.307 TMEM163 Zornitza Stark Classified gene: TMEM163 as Green List (high evidence)
Mendeliome v1.307 TMEM163 Zornitza Stark Gene: tmem163 has been classified as Green List (High Evidence).
Mendeliome v1.306 NBAS Zornitza Stark Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483 to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800; Infantile liver failure syndrome 2, MIM# 616483; Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Mendeliome v1.305 NBAS Zornitza Stark Publications for gene: NBAS were set to 31761904
Mendeliome v1.304 NBAS Zornitza Stark edited their review of gene: NBAS: Added comment: PMID 35902954 - Biallelic NBAS variants identifed in three HLH patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-defcient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus.; Changed publications: 31761904, 35902954; Changed phenotypes: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, Infantile liver failure syndrome 2, MIM# 616483, Haemophagocytic lymphohistiocytosis (HLH), MONDO:0015541
Mendeliome v1.304 TYMS Zornitza Stark Marked gene: TYMS as ready
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.304 TYMS Zornitza Stark Classified gene: TYMS as Amber List (moderate evidence)
Mendeliome v1.304 TYMS Zornitza Stark Gene: tyms has been classified as Amber List (Moderate Evidence).
Mendeliome v1.303 TYMS Zornitza Stark reviewed gene: TYMS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita MONDO:0015780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.303 COX11 Zornitza Stark Classified gene: COX11 as Green List (high evidence)
Mendeliome v1.303 COX11 Zornitza Stark Gene: cox11 has been classified as Green List (High Evidence).
Mendeliome v1.302 COX11 Zornitza Stark gene: COX11 was added
gene: COX11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551
Phenotypes for gene: COX11 were set to Mitochondrial disease (MONDO:0044970), COX11-related
Review for gene: COX11 was set to GREEN
Added comment: PMID: 36030551
- Biallelic variants in COX11 associated with infantile-onset mitochondrial encephalopathies in two unrelated consanguineous families, one with homozygous missense variant, another with homozygous frameshift variant.
- Functional studies supported pathogenicity of the missense variant, and showed that mutant COX11 fibroblasts had decreased ATP levels which could be rescued by CoQ10.
- RNA studies suggested the mutant transcript with p.(Val12Glyfs*21) is not degraded by nonsense mediated decay.
Sources: Literature
Mendeliome v1.301 SARS Zornitza Stark Publications for gene: SARS were set to 28236339; 34570399; 35790048
Mendeliome v1.300 TMEM147 Zornitza Stark Marked gene: TMEM147 as ready
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.300 TMEM147 Zornitza Stark Classified gene: TMEM147 as Green List (high evidence)
Mendeliome v1.300 TMEM147 Zornitza Stark Gene: tmem147 has been classified as Green List (High Evidence).
Mendeliome v1.299 SAT1 Zornitza Stark Phenotypes for gene: SAT1 were changed from to Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Keratosis follicularis spinulosa decalvans
Mendeliome v1.298 SAT1 Zornitza Stark Publications for gene: SAT1 were set to
Mendeliome v1.297 SAT1 Zornitza Stark Mode of inheritance for gene: SAT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.296 SAT1 Zornitza Stark Classified gene: SAT1 as Amber List (moderate evidence)
Mendeliome v1.296 SAT1 Zornitza Stark Gene: sat1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.295 CEP104 Zornitza Stark Phenotypes for gene: CEP104 were changed from Joubert syndrome 25, MIM# 616781; MONDO:0014770 to Joubert syndrome 25, MIM# 616781; MONDO:0014770; Neurodevelopmental disorder; MONDO:0014770, CEP104-related
Mendeliome v1.294 CEP104 Zornitza Stark Publications for gene: CEP104 were set to 26477546
Mendeliome v1.293 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835; Diamond-Blackfan anemia (MONDO:0015253)
Mendeliome v1.292 GATA1 Zornitza Stark Publications for gene: GATA1 were set to
Mendeliome v1.291 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: PMID 36029112: De novo GATA1 initiation codon variant (c.3G>A) identified in a Diamond-Blackfan Anaemia patient. Functional evidence showed that the variant does not affect the GATA1 mRNA but brings about a shorter GATA1 isoform (GATA1s) and reduced full-length functional GATA1 protein (GATA1fl), thereby contributing to an erythropoietic defect. Four other GATA1 variants (c.2T>C, c.220G>C, c.220delG, c.220+2T>C) found in eight families have been described as DBA phenotype.; Changed publications: 36029112; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835, Diamond-Blackfan anemia (MONDO:0015253)
Mendeliome v1.291 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.291 LGI3 Zornitza Stark Phenotypes for gene: LGI3 were changed from Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi to Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Mendeliome v1.290 LGI3 Zornitza Stark Classified gene: LGI3 as Green List (high evidence)
Mendeliome v1.290 LGI3 Zornitza Stark Gene: lgi3 has been classified as Green List (High Evidence).
Mendeliome v1.289 LGI3 Zornitza Stark reviewed gene: LGI3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, LGI3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.289 TMEM147 Naomi Baker gene: TMEM147 was added
gene: TMEM147 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to PMID: 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder (MONDO:0700092), TMEM147-related
Review for gene: TMEM147 was set to GREEN
Added comment: PMID: 36044892; Twelve different variants reported in 23 affected individuals from 15 unrelated families with biallelic variants. All individuals had global developmental delay and intellectual disability. Consistent facial dysmorphisms included coarse facies, prominent forehead, board depressed nasal root, tented mouth, long smooth philtrum, and low-set ears. In vitro studies of missense variants demonstrated accelerated protein degradation via the autophagy-lysosomal pathway, while analysis of primary fibroblasts and granulocytes provided functional evidence of ER and nuclear envelope dysfunction.
Sources: Literature
Mendeliome v1.289 SARS Ee Ming Wong reviewed gene: SARS: Rating: RED; Mode of pathogenicity: Other; Publications: 36041817; Phenotypes: neurodevelopmental disorder, MONDO#070009, SARS1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.289 ADAMTS15 Zornitza Stark Marked gene: ADAMTS15 as ready
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Mendeliome v1.289 ADAMTS15 Zornitza Stark Classified gene: ADAMTS15 as Green List (high evidence)
Mendeliome v1.289 ADAMTS15 Zornitza Stark Gene: adamts15 has been classified as Green List (High Evidence).
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Mendeliome v1.288 CAPRIN1 Zornitza Stark Classified gene: CAPRIN1 as Green List (high evidence)
Mendeliome v1.288 CAPRIN1 Zornitza Stark Gene: caprin1 has been classified as Green List (High Evidence).
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.287 CBLB Alison Yeung Classified gene: CBLB as Green List (high evidence)
Mendeliome v1.287 CBLB Alison Yeung Gene: cblb has been classified as Green List (High Evidence).
Mendeliome v1.286 CBLB Alison Yeung gene: CBLB was added
gene: CBLB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CBLB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBLB were set to 36006710
Phenotypes for gene: CBLB were set to Autoimmune disease, MONDO:0007179
Review for gene: CBLB was set to GREEN
Added comment: Distinct homozygous mutations in CBLB were identified in three unrelated children with early onset autoimmunity. Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient's p.H285L mutation, had T and B cell hyper-proliferation in response to antigen receptor cross-linking.
Sources: Literature
Mendeliome v1.285 TYMS Lucy Spencer gene: TYMS was added
gene: TYMS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TYMS was set to Other
Publications for gene: TYMS were set to 35931051
Phenotypes for gene: TYMS were set to Dyskeratosis congenita MONDO:0015780
Review for gene: TYMS was set to RED
Added comment: 8 families with dyskeratosis congenita and heterozygous variants in TYMS. 4 PTCs, 2 missense and 1 splice (2 families had the same frameshift). However in all families 1 unaffected parent was also heterozygous for the same TYSM variant.

The other parent in 3 of these families was then shown to carry a heterozygous variant in ENOSF1 which each affected child was also heterozygous for. ENOSF1 has been shown to modify TYMS expression at the RNA level by acting as an antisense molecule to TYMS. ENOSF1 partially overlaps TYMS on chromosome 18 and is transcribed in the opposite direction to TYMS. This paper is suggesting digenic inheritance.

The TYMS wild type parent from another family was seen to have a TYMSOS variant which was also observed along with the TYMS variant in their 2 affected children.

Immunoblotting showed a stark reduction in TYMS protein level in the cells of affected probands when compared to the parent carrier, wild-type parent, and the controls.

Lymphoblastoid cells from affected probands have severe TYMS deficiency, altered cellular deoxyribonucleotide triphosphate pools, and hypersensitivity to the TYMS-specific inhibitor 5-fluorouracil. These defects in the nucleotide metabolism pathway resulted in genotoxic stress, defective transcription, and abnormal telomere maintenance. Gene-rescue studies in cells from affected probands revealed that post-transcriptional epistatic silencing of TYMS is occurring via elevated ENOSF1.
Sources: Literature
Mendeliome v1.285 CEP104 Belinda Chong reviewed gene: CEP104: Rating: GREEN; Mode of pathogenicity: None; Publications: 34196201, 35359234; Phenotypes: CEP104 Neurodevelopmental disorder, MONDO:0014770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.285 LGI3 Melanie Marty edited their review of gene: LGI3: Changed phenotypes: Global developmental delay, Intellectual disability, Distal deformities, Diminished reflexes, Facial myokymia, Hyporeflexia/areflexia
Mendeliome v1.285 HNRNPH1 Hazel Phillimore changed review comment from: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2).
In gnomAD, there are very few LOF variants. (LOF shows pLI = 1).
The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma.; to: PMID: 35989590; Ouyang, J. et al. (2022): Two loss of function variants c.2dup, p.(M1?) and c.121dup, p.(Q41Pfs*20), were found in two individuals with early onset high myopia. They were in cohort of 928 probands with early onset high myopia. The pedigrees for these probands indicate that no other relatives were affected. However, it does not appear that any relatives were tested for these variants. These variants were reported to be absent in gnomAD. Note: there is actually 1 heterozygote for an alternative variant that is predicted to cause p.(Met1?) in gnomADv2.
In gnomAD, there are very few LOF variants. (LOF shows pLI = 1).
The group also studied knockdown of this gene in zebrafish, which resulted in ocular coloboma.
Mendeliome v1.285 HNRNPH1 Hazel Phillimore reviewed gene: HNRNPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35989590; Phenotypes: early onset high myopia, blindness; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.285 TMEM163 Teresa Zhao changed review comment from: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.
Sources: Literature; to: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures.
Sources: Literature
Mendeliome v1.285 MET Zornitza Stark Phenotypes for gene: MET were changed from Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884 to Arthrogryposis, distal, type 11 (MIM#620019), AD; Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884
Mendeliome v1.284 MET Zornitza Stark Publications for gene: MET were set to
Mendeliome v1.283 MET Zornitza Stark changed review comment from: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; to: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.

AMBER for this association
Mendeliome v1.283 MET Zornitza Stark edited their review of gene: MET: Added comment: PMID 30777867:
Four-generation Chinese arthrogryposis pedigree with only upper limb involvement. MET c.3701A>G p.Y1234C segregated as heterozygous in 11 affected family members and was absent from 12 unaffected family members. Variant is absent from gnomad. Functional studies showed this variant caused failure of phosphorylation and loss of tyrosine kinase activity of MET receptor. A mouse model was also created with this variant, mutated mice were found to be smaller than WT mice and had reduced myofibres. These mouse models also had defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts. Phenotypes in this family included camptodactyly, absent flexion crease, and limited forearm supination.; Changed publications: 30777867
Mendeliome v1.283 TMEM163 Teresa Zhao gene: TMEM163 was added
gene: TMEM163 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM163 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM163 were set to PMID: 35953447
Phenotypes for gene: TMEM163 were set to Hypomyelinating leukodystrophy
Review for gene: TMEM163 was set to GREEN
Added comment: Four unrelated families with a hypomyelinating leukodystrophy phenotype. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant.

All have global developmental delay, three of them have seizures and two have ID.
Sources: Literature
Mendeliome v1.283 LGI3 Melanie Marty gene: LGI3 was added
gene: LGI3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to PMID: 35948005
Phenotypes for gene: LGI3 were set to Global developmental delay; Intellectual disability; Distal deformities; Diminished reflexes; Facial myokymia; Hyporeflexia/areflexi
Review for gene: LGI3 was set to GREEN
Added comment: Sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3.
Lgi3-null mice showed reduced and mis-local-ized Kv1 channel complexes in myelinated peripheral axons.
Sources: Literature
Mendeliome v1.283 NOTCH1 Zornitza Stark Phenotypes for gene: NOTCH1 were changed from Adams-Oliver syndrome 5 (MIM#616028) to Adams-Oliver syndrome 5 (MIM#616028); Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Mendeliome v1.282 NOTCH1 Zornitza Stark Publications for gene: NOTCH1 were set to 25963545; 25132448
Mendeliome v1.281 NOTCH1 Zornitza Stark Mode of pathogenicity for gene: NOTCH1 was changed from to Other
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.280 BUD13 Alison Yeung Classified gene: BUD13 as Amber List (moderate evidence)
Mendeliome v1.280 BUD13 Alison Yeung Gene: bud13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.279 BUD13 Alison Yeung gene: BUD13 was added
gene: BUD13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUD13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUD13 were set to 35670808
Phenotypes for gene: BUD13 were set to Lipodystrophy, MONDO:0006573
Review for gene: BUD13 was set to AMBER
Added comment: 5 individuals with a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life, 2 are adults with normal intellectual development. All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13. Individuals from only two Algerian families.
Sources: Literature
Mendeliome v1.278 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to 30544257
Mendeliome v1.277 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.276 SAT1 Ee Ming Wong reviewed gene: SAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35977808; Phenotypes: Systemic lupus erythematosus, MONDO:0007915, SAT1-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v1.276 NOTCH1 Chern Lim changed review comment from: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Missense and small inframe insertion variants in the negative regulatory region.; to: PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.
Mendeliome v1.276 ADAMTS15 Naomi Baker changed review comment from: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature; to: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: contractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.276 ADAMTS15 Naomi Baker gene: ADAMTS15 was added
gene: ADAMTS15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to PMID: 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis (MONDO:0008779), ADMATS15-related
Review for gene: ADAMTS15 was set to GREEN
Added comment: PMID: 35962790; Four different homozygous variants identified in five affected individuals from four unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. All patients also had a mild appearance of fetal finger pads and clinodactyly of the fifth finger. Other reported phenotypes include: ontractures of knee, Achilles tendon, and ankle (4/5), spine involvement (kyphoscoliosis and/or spinal stiffness) (4/5), and orthodontic features (small mouth, dental crowding, missing teeth, or arched palate) (4/5).
Sources: Literature
Mendeliome v1.276 NOTCH1 Chern Lim edited their review of gene: NOTCH1: Changed phenotypes: Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related
Mendeliome v1.276 CAPRIN1 Paul De Fazio gene: CAPRIN1 was added
gene: CAPRIN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAPRIN1 were set to 35979925
Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092
Review for gene: CAPRIN1 was set to GREEN
gene: CAPRIN1 was marked as current diagnostic
Added comment: 12 individuals reported with ID and language impairment. Other features included seizures (4 individuals), hands and feet malformations (5 individuals), breathing problems (6 individuals), ocular problems (4 individuals) and hearing problems (3 individuals).

All of the variants were nonsense (NMD-predicted) or splicing variants. 10 were de novo, 1 was inherited from an affected father. Functional studies supported pathogenicity.
Sources: Literature
Mendeliome v1.276 LHX8 Alison Yeung gene: LHX8 was added
gene: LHX8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LHX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX8 were set to 36029299
Phenotypes for gene: LHX8 were set to Inherited premature ovarian failure, MONDO:0019852, LHX8-related
Review for gene: LHX8 was set to GREEN
Added comment: Heterozygous LOF variants identified in 6 families with premature ovarian failure due to oocyte maturation arrest.
Sources: Literature
Mendeliome v1.275 NOTCH1 Chern Lim reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35947102; Phenotypes: leukoencephalopathy and calcifications; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.275 GRIN2A Teresa Zhao reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35983985; Phenotypes: Epilepsy, focal, with speech disorder and with or without impaired intellectual development (MIM#245570); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.275 LEF1 Zornitza Stark Phenotypes for gene: LEF1 were changed from Ectodermal dysplasia, no OMIM# yet to Syndromic disease, MONDO:0002254, LEF1-related
Mendeliome v1.274 LEF1 Zornitza Stark Publications for gene: LEF1 were set to 32022899
Mendeliome v1.273 LEF1 Zornitza Stark Mode of inheritance for gene: LEF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.272 LEF1 Zornitza Stark Classified gene: LEF1 as Green List (high evidence)
Mendeliome v1.272 LEF1 Zornitza Stark Gene: lef1 has been classified as Green List (High Evidence).
Mendeliome v1.271 LEF1 Zornitza Stark edited their review of gene: LEF1: Added comment: Monoallelic variants in LEF1 reported in 11 affected individuals from 4 unrelated families, and a biallelic variant reported in an affected individual from a consanguineous family. The phenotypic spectrum included various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Haploinsufficiency or loss of DNA binding postulated to be responsible for a mild to moderate phenotype, whereas loss of β-catenin binding caused by biallelic variants postulated to be associated with a severe phenotype.; Changed rating: GREEN; Changed publications: 32022899, 35583550; Changed phenotypes: Syndromic disease, MONDO:0002254, LEF1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.271 REEP1 Zornitza Stark Phenotypes for gene: REEP1 were changed from Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy to Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250
Mendeliome v1.270 REEP1 Zornitza Stark reviewed gene: REEP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.270 CCDC82 Zornitza Stark Gene: ccdc82 has been classified as Green List (High Evidence).
Mendeliome v1.270 CCDC82 Zornitza Stark Phenotypes for gene: CCDC82 were changed from Intellectual disability and spastic paraparesis, no OMIM # to Neurodevelopmental disorder, MONDO:0700092, CCDC82-related
Mendeliome v1.269 CCDC82 Zornitza Stark Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Mendeliome v1.268 CCDC82 Zornitza Stark reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CCDC82-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.268 NPNT Zornitza Stark Marked gene: NPNT as ready
Mendeliome v1.268 NPNT Zornitza Stark Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.268 NPNT Zornitza Stark Phenotypes for gene: NPNT were changed from Renal agenesis, no OMIM # to Renal agenesis, MONDO:0018470, NPNT-related
Mendeliome v1.267 NPNT Zornitza Stark Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Mendeliome v1.266 NPNT Zornitza Stark reviewed gene: NPNT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.266 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Skeletal dysplasia, MONDO:0018230 to Skeletal dysplasia, MONDO:0018230, KIF5B-related; Kyphomelic dysplasia
Mendeliome v1.265 KIF5B Zornitza Stark Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.265 KIF5B Zornitza Stark Phenotypes for gene: KIF5B were changed from Kyphomelic dysplasia, no OMIM # to Skeletal dysplasia, MONDO:0018230
Mendeliome v1.264 KIF5B Zornitza Stark reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.264 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome, type VI, MIM# 620022; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v1.263 COL9A3 Zornitza Stark edited their review of gene: COL9A3: Changed phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969, Stickler syndrome, type VI, MIM# 620022, Deafness
Mendeliome v1.263 LNPK Chirag Patel Classified gene: LNPK as Green List (high evidence)
Mendeliome v1.263 LNPK Chirag Patel Gene: lnpk has been classified as Green List (High Evidence).
Mendeliome v1.262 LNPK Chirag Patel reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35599435; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM# 618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.262 CCDC82 Chirag Patel Classified gene: CCDC82 as Green List (high evidence)
Mendeliome v1.262 CCDC82 Chirag Patel Gene: ccdc82 has been classified as Green List (High Evidence).
Mendeliome v1.261 CCDC82 Chirag Patel gene: CCDC82 was added
gene: CCDC82 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC82 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC82 were set to PMID: 35373332, 35118659, 27457812
Phenotypes for gene: CCDC82 were set to Intellectual disability and spastic paraparesis, no OMIM #
Review for gene: CCDC82 was set to GREEN
Added comment: 4 consanguineous families with 9 affected individuals with developmental delay/intellectual disability, and 2 families had spasticity and 1 had epilepsy. WES identified 3 homozgyous truncating variants, segregating with disease and parents as carriers. No functional studies.
Sources: Literature
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.260 NPNT Chirag Patel Classified gene: NPNT as Green List (high evidence)
Mendeliome v1.260 NPNT Chirag Patel Gene: npnt has been classified as Green List (High Evidence).
Mendeliome v1.259 NPNT Chirag Patel gene: NPNT was added
gene: NPNT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to PMID: 35246978, 34049960, 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, no OMIM #
Review for gene: NPNT was set to GREEN
Added comment: 3 consanguineous families with multiple affecteds with bilateral renal agenesis. Whole-exome sequencing (WES)-based homozygosity mapping identified 2 homozygous truncating variants. Reverse transcription polymerase chain reaction data showing complete nonsense-mediated decay of the NPNT transcript. Loss of nephronectin (NPNT) is known to lead to failure of metanephric kidney development with resulting renal agenesis in murine models.
Sources: Literature
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.258 KIF5B Chirag Patel Classified gene: KIF5B as Green List (high evidence)
Mendeliome v1.258 KIF5B Chirag Patel Gene: kif5b has been classified as Green List (High Evidence).
Mendeliome v1.257 KIF5B Chirag Patel gene: KIF5B was added
gene: KIF5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to PMID: 35342932
Phenotypes for gene: KIF5B were set to Kyphomelic dysplasia, no OMIM #
Review for gene: KIF5B was set to GREEN
Added comment: 4 individuals with Kyphomelic dysplasia (severe bowing of the limbs, sharp angulation of the femora and humeri, short stature, narrow thorax, distinctive facial features, and neonatal respiratory distress. WES found de novo heterozygous missense variants in KIF5B encoding kinesin-1 heavy chain. All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. No functional studies of variants. Previously 2 animal model experiments showed that loss of function of KIF5B can cause kyphomelic dysplasia. First, chondrocyte-specific knockout of Kif5b in mice was shown to produce a disorganized growth plate, leading to bone deformity. Second, double mutants disrupting the two zebrafish kif5b caused abnormal skeletal morphogenesis and the curvature of Meckel's and ceratohyal cartilages.
Sources: Literature
Mendeliome v1.256 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from neurodevelopmental disorder MONDO:0700092; FBXW7-related neurodevelopmental syndrome; Wilms tumor MONDO:0006058 to Developmental delay, hypotonia, and impaired language, MIM# 620012; Wilms tumour predisposition
Mendeliome v1.255 FBXW7 Zornitza Stark edited their review of gene: FBXW7: Changed phenotypes: Developmental delay, hypotonia, and impaired language, MIM# 620012, Wilms tumour predisposition
Mendeliome v1.255 MDFIC Zornitza Stark Phenotypes for gene: MDFIC were changed from Hydrops fetalis MONDO:0015193 to Lymphatic malformation 12, MIM# 620014
Mendeliome v1.254 MDFIC Zornitza Stark reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphatic malformation 12, MIM# 620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.254 ACADS Zornitza Stark Classified gene: ACADS as Amber List (moderate evidence)
Mendeliome v1.254 ACADS Zornitza Stark Gene: acads has been classified as Amber List (Moderate Evidence).
Mendeliome v1.253 ACADS Zornitza Stark changed review comment from: Definitive by ClinGen.; to: Definitive by ClinGen. However, largely just causes a biochemical abnormality, and association with clinical disease is debated.
Mendeliome v1.253 ACADS Zornitza Stark edited their review of gene: ACADS: Changed rating: AMBER
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.253 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Mendeliome v1.253 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Mendeliome v1.252 FOCAD Zornitza Stark gene: FOCAD was added
gene: FOCAD was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to 35864190
Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991
Review for gene: FOCAD was set to GREEN
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review
Mendeliome v1.251 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, TAF4-related
Mendeliome v1.250 TAF4 Zornitza Stark Publications for gene: TAF4 were set to 33875846; 28191890
Mendeliome v1.249 TAF4 Zornitza Stark Classified gene: TAF4 as Green List (high evidence)
Mendeliome v1.249 TAF4 Zornitza Stark Gene: taf4 has been classified as Green List (High Evidence).
Mendeliome v1.248 TAF4 Zornitza Stark edited their review of gene: TAF4: Changed rating: GREEN; Changed publications: 33875846, 28191890, 35904126; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF4-related
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.248 ZMYND8 Zornitza Stark Classified gene: ZMYND8 as Green List (high evidence)
Mendeliome v1.248 ZMYND8 Zornitza Stark Gene: zmynd8 has been classified as Green List (High Evidence).
Mendeliome v1.247 ZMYND8 Zornitza Stark gene: ZMYND8 was added
gene: ZMYND8 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures
Review for gene: ZMYND8 was set to GREEN
Added comment: Dias et al (2022 - PMID: 35916866) describe the phenotype of 11 unrelated individuals with monoallelic de novo (or suspected de novo) missense (N=9) or truncating (N=2) ZMYND8 variants. One of these subjects was previously reported by Suzuki et al (2020 - PMID: 32530565).

Features included speech delay/language difficulties (9/11), motor delay (9/11), ID (in 10/11 - profound in 1, moderate in 2), CHD (7/11 - PDA, VSD, ASD, pulmonary stenosis, etc), hearing or vision impairment (7/11). Seizures were reported in few (in text 5/11, table 2/11). Variable non-familial facial features were present in (9/11).

As the authors discuss, ZMYND8 encodes a multidomain protein playing a role in transcription regulation, chromatin remodeling, regulation of super enhancers, DNA damage response/tumor suppression.

The protein is broadly expressed in brain and shows highest expression in early development.

Molecular modeling and/or a yeast two-hybrid system were suggestive of disrupted interaction of ZMYND8 with Drebrin (missense variants in PWWP domain) or GATAD2A (variants in MYND domain).

Neuronal Zmynd8 knockdown in Drosophila resulted in deficits in habituation learning.
Sources: Expert Review
Mendeliome v1.246 TRAC Zornitza Stark Tag founder tag was added to gene: TRAC.
Mendeliome v1.246 TRAC Seb Lunke Classified gene: TRAC as Amber List (moderate evidence)
Mendeliome v1.246 TRAC Seb Lunke Added comment: Comment on list classification: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001) Also note annotation issues in certain variant curation and annotation tools.
Mendeliome v1.246 TRAC Seb Lunke Gene: trac has been classified as Amber List (Moderate Evidence).
Mendeliome v1.245 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from Neurodevelopmental disorder MONDO:0700092, PAX5-related to Neurodevelopmental disorder MONDO:0700092, PAX5-related; Hypogammaglobulinaemia
Mendeliome v1.244 PAX5 Zornitza Stark Publications for gene: PAX5 were set to 35094443; 31452935; 28263302; 25418537; 8001127; 27626380
Mendeliome v1.243 PAX5 Zornitza Stark Mode of inheritance for gene: PAX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.242 PAX5 Zornitza Stark reviewed gene: PAX5: Rating: AMBER; Mode of pathogenicity: None; Publications: 35947077; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PAX5-related, Hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.242 PRIM1 Zornitza Stark Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Mendeliome v1.241 PRIM1 Zornitza Stark edited their review of gene: PRIM1: Changed phenotypes: Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, MIM# 620005
Mendeliome v1.241 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, MIM# 616920 to Heart and brain malformation syndrome, MIM# 616920; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.240 SMG9 Zornitza Stark Publications for gene: SMG9 were set to 27018474; 31390136
Mendeliome v1.239 SMG9 Zornitza Stark edited their review of gene: SMG9: Added comment: PMID 35087184: 5 individuals from 3 unrelated Finnish families reported with same homozygous missense variant (founder effect) and predominantly neurological phenotype. Uncertain if this is a distinct disorder or part of a spectrum with the previously reported cases.; Changed publications: 27018474, 31390136, 35087184; Changed phenotypes: Heart and brain malformation syndrome, MIM# 616920, Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies, MIM# 619995
Mendeliome v1.239 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic disease, MONDO:0002254, THUMPD1-related to Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989
Mendeliome v1.238 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with speech delay and variable ocular anomalies, MIM# 619989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.238 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.237 OTULIN Zornitza Stark edited their review of gene: OTULIN: Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, MIM# 619986
Mendeliome v1.237 TAF4 Ee Ming Wong reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846, 28191890, 35904126; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.237 SPTBN5 Zornitza Stark Phenotypes for gene: SPTBN5 were changed from Sacral agenesis; congenital anomalies to Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related; Sacral agenesis; congenital anomalies
Mendeliome v1.236 SPTBN5 Zornitza Stark Publications for gene: SPTBN5 were set to 32732226; 28007035
Mendeliome v1.235 SPTBN5 Zornitza Stark Mode of inheritance for gene: SPTBN5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.234 SPTBN5 Zornitza Stark Classified gene: SPTBN5 as Green List (high evidence)
Mendeliome v1.234 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Green List (High Evidence).
Mendeliome v1.233 SPTBN5 Zornitza Stark changed review comment from: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature; to: Bi-allelic variants: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v1.233 SPTBN5 Zornitza Stark edited their review of gene: SPTBN5: Added comment: Monoallelic variants:
- Four probands from unrelated families (1x Pakistani and 3x Italian) with de novo heterozygous SPTBN5 variants
- 3x missense variants and 1x LoF variant were reported
- Phenotypes include intellectual disability (mild to severe), aggressive tendencies and variable features such as craniofacial and physical dysmorphisms, autistic behavior, and gastroesophageal reflux; Changed rating: GREEN; Changed publications: 35782384, 32732226, 28007035; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SPTBN5-related, Sacral agenesis, congenital anomalies; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.233 CPS1 Zornitza Stark Phenotypes for gene: CPS1 were changed from to Carbamoylphosphate synthetase I deficiency MIM#237300
Mendeliome v1.232 CPS1 Zornitza Stark Mode of inheritance for gene: CPS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.231 CPS1 Zornitza Stark reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Pulmonary hypertension, neonatal, susceptibility to} 615371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.231 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Mendeliome v1.230 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085
Mendeliome v1.229 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.228 OTULIN Zornitza Stark changed review comment from: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.; to: Bi-allelic variants: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.
Mendeliome v1.228 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: PMID 35587511: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.; Changed publications: 27523608, 27559085, 35587511; Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Susceptibility to infection with Staphylococcus aureus, Hereditary predisposition to infections, MONDO:0015979, OTULIN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.228 NOX1 Zornitza Stark gene: NOX1 was added
gene: NOX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis.

The variant reported in PMID 32064493 is present in 6 hets in gnomad.
Sources: Literature
Mendeliome v1.227 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291 to Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291
Mendeliome v1.226 BICD2 Zornitza Stark Publications for gene: BICD2 were set to 23664116; 23664119; 23664120; 27751653; 28635954; 30054298; 29528393
Mendeliome v1.225 BICD2 Zornitza Stark Mode of inheritance for gene: BICD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.224 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.223 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.222 SARS Ain Roesley Publications for gene: SARS were set to 28236339; 34570399
Mendeliome v1.222 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Mendeliome v1.222 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Mendeliome v1.222 SARS Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related
Mendeliome v1.221 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Phenotypes for gene: PSMC1 were changed from spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mendeliome v1.220 SARS Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.220 PSMC1 Zornitza Stark Mode of pathogenicity for gene: PSMC1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.219 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Mendeliome v1.219 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.218 PSMC1 Zornitza Stark edited their review of gene: PSMC1: Changed phenotypes: Syndromic disease MONDO:0002254, PSMC1-related
Mendeliome v1.218 PSMC1 Zornitza Stark commented on gene: PSMC1: Single family only, homozygous missense variant.
Mendeliome v1.218 PSMC1 Zornitza Stark reviewed gene: PSMC1: Rating: RED; Mode of pathogenicity: None; Publications: 35861243; Phenotypes: Syndromic disease MONDO:0002254, PSMC1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.218 WARS Seb Lunke Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783.
Mendeliome v1.217 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.217 WARS Seb Lunke Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related
Mendeliome v1.216 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Mendeliome v1.216 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.215 WARS Seb Lunke Mode of inheritance for gene: WARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.214 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Mendeliome v1.213 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.213 BICD2 Lucy Spencer reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35896821; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.213 KIF15 Krithika Murali reviewed gene: KIF15: Rating: AMBER; Mode of pathogenicity: None; Publications: 28150392; Phenotypes: ?Braddock-Carey syndrome 2 - MIM#619981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.213 WARS Anna Ritchie reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35815345, PMID: 35790048; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), WARS-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.213 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.212 KIF15 Krithika Murali Deleted their review
Mendeliome v1.212 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mode of pathogenicity for gene: PSMC1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PSMC1 was set to AMBER
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Mendeliome v1.212 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to GREEN
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.211 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive
Sources: Literature
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Cystic renal disease MONDO:0002473, ALG5-related, Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Mendeliome v1.208 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Cystic renal disease MONDO:0002473, ALG5-related
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Mendeliome v1.208 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Mendeliome v1.208 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.208 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Mendeliome v1.208 RFC1 Ain Roesley Publications for gene: RFC1 were set to 30926972
Mendeliome v1.208 RFC1 Ain Roesley Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Mendeliome v1.207 RFC1 Ain Roesley Classified gene: RFC1 as Amber List (moderate evidence)
Mendeliome v1.207 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.206 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Mendeliome v1.206 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.206 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.205 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.205 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.204 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Mendeliome v1.204 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Mendeliome v1.203 EHHADH Zornitza Stark Classified gene: EHHADH as Amber List (moderate evidence)
Mendeliome v1.203 EHHADH Zornitza Stark Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.202 EHHADH Zornitza Stark edited their review of gene: EHHADH: Added comment: https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf

Second case report, same variant, de novo. Also, experimental evidence. Assessed as MODERATE by ClinGen.; Changed rating: AMBER
Mendeliome v1.202 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis 6 - MIM#607200 to Thyroid dyshormonogenesis 6 - MIM#607200; Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Mendeliome v1.201 DUOX2 Zornitza Stark Publications for gene: DUOX2 were set to
Mendeliome v1.200 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.199 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Mendeliome v1.199 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.198 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35429653, 27373512, 26301257, 28683258; Phenotypes: Inflammatory bowel disease, MONDO:0005265, DUOX2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.198 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.198 CWH43 Zornitza Stark Phenotypes for gene: CWH43 were changed from normal pressure hydrocephalus to Hydrocephalus MONDO:0001150, CWH43-related
Mendeliome v1.197 CWH43 Zornitza Stark Classified gene: CWH43 as Red List (low evidence)
Mendeliome v1.197 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.196 CWH43 Zornitza Stark Tag cnv tag was added to gene: CWH43.
Mendeliome v1.196 CWH43 Zornitza Stark reviewed gene: CWH43: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus MONDO:0001150, CWH43-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.196 CWH43 Anna Le Fevre gene: CWH43 was added
gene: CWH43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to PMID: 33459505; 34380733
Phenotypes for gene: CWH43 were set to normal pressure hydrocephalus
Penetrance for gene: CWH43 were set to Incomplete
Review for gene: CWH43 was set to AMBER
Added comment: Sources: Literature
Mendeliome v1.196 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Mendeliome v1.196 ADGRA3 Zornitza Stark gene: ADGRA3 was added
gene: ADGRA3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ADGRA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRA3 were set to 23105016
Phenotypes for gene: ADGRA3 were set to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Review for gene: ADGRA3 was set to RED
Added comment: Only one report of a missense that is a VUS identified as a candidate through autozygome analysis (PMID: 23105016)
Sources: Expert Review
Mendeliome v1.195 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.194 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.194 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from Intellectual disability to Snijders Blok-Fisher syndrome MIM#618604
Mendeliome v1.193 POU3F3 Zornitza Stark edited their review of gene: POU3F3: Changed phenotypes: Snijders Blok-Fisher syndrome MIM#618604
Mendeliome v1.193 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM#618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Mendeliome v1.192 ROBO4 Zornitza Stark Publications for gene: ROBO4 were set to 30455415
Mendeliome v1.191 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Mendeliome v1.191 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.190 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy to leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Mendeliome v1.189 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to 11835386; 26285592; 15776425; 18263758; 25843247; 25761052; 30014503
Mendeliome v1.188 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.187 EIF2B1 Zornitza Stark reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.187 MCM10 Zornitza Stark Publications for gene: MCM10 were set to 32865517; 33712616
Mendeliome v1.186 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Mendeliome v1.186 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.185 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: PMID 33712616: further functional validation.; Changed rating: AMBER; Changed publications: 32865517, 33712616, 33712616
Mendeliome v1.185 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset; Immune dysregulation
Mendeliome v1.184 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to 21548011; 26981933; 29889099; 31057532; 7923373; 11805317
Mendeliome v1.183 IKZF1 Zornitza Stark edited their review of gene: IKZF1: Added comment: PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.; Changed publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317, 35333544; Changed phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset, Immune dysregulation
Mendeliome v1.183 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation
Mendeliome v1.182 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454
Mendeliome v1.181 IKZF2 Zornitza Stark Mode of inheritance for gene: IKZF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.180 IKZF2 Zornitza Stark edited their review of gene: IKZF2: Added comment: Iranian male with homozygous missense variant with recurrent infection, hypogammaglobulinaemia. Extends inheritance to AR. Supportive functional data.; Changed publications: 34920454, 34826259; Changed phenotypes: Immunodeficiency, MONDO:0021094, IKZF2-related, Immune dysregulation; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.180 TMEM63C Zornitza Stark Marked gene: TMEM63C as ready
Mendeliome v1.180 TMEM63C Zornitza Stark Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.180 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Mendeliome v1.179 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.179 ROBO4 Elena Savva reviewed gene: ROBO4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:30455415, 32748548; Phenotypes: Aortic valve disease 8 MIM#618496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.179 EIF2B1 Elena Savva reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31882561; Phenotypes: Leukoencephalopathy with vanishing white matter MIM#603896, permanent neonatal/early onset diabetes and transient liver dysfunction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.179 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 PAK2 Zornitza Stark Phenotypes for gene: PAK2 were changed from Knobloch 2 syndrome to Knobloch 2 syndrome, MIM#618458
Mendeliome v1.177 INPP5E Zornitza Stark Publications for gene: INPP5E were set to 19668216; 32139166; 29230161; 29052317; 27998989; 27401686; 19668215
Mendeliome v1.176 INPP5E Zornitza Stark edited their review of gene: INPP5E: Added comment: Additional MORM family reported in PMID 34211432, hmz LoF.; Changed publications: 19668216, 32139166, 29230161, 29052317, 27998989, 27401686, 19668215, 34211432
Mendeliome v1.176 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Mendeliome v1.176 WASL Zornitza Stark gene: WASL was added
gene: WASL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to 33571872
Phenotypes for gene: WASL were set to Parkinson's disease, MONDO:0005180, WASL-related
Review for gene: WASL was set to RED
Added comment: Single family reported, where bi-allelic variants segregated with PD in three affected individuals.
Sources: Literature
Mendeliome v1.175 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia (MIM#212065) to Congenital disorder of glycosylation, type Ia (MIM#212065); Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Mendeliome v1.174 PMM2 Zornitza Stark Publications for gene: PMM2 were set to 28108845
Mendeliome v1.173 PMM2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: CDG: Well established gene-disease association.
Mendeliome v1.173 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Association with HIPKD:
Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed publications: 28108845, 28373276, 32595772; Changed phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065), Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Mendeliome v1.173 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.172 SLCO2A1 Zornitza Stark Publications for gene: SLCO2A1 were set to 23509104; 27134495; 33852188; 22331663; 27134495
Mendeliome v1.171 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Added comment: PMID 29313109: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology. Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.; Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495, 29313109; Changed phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441, Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.171 CTR9 Zornitza Stark Phenotypes for gene: CTR9 were changed from Neurodevelopmental disorder (MONDO:0700092), CTR9 related to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Familial Wilms tumour, MONDO:0006058, CTR9-related
Mendeliome v1.170 CTR9 Zornitza Stark Publications for gene: CTR9 were set to PMID: 35499524
Mendeliome v1.169 CTR9 Zornitza Stark reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25099282, 29292210; Phenotypes: Familial Wilms tumour, MONDO:0006058, CTR9-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.169 C20orf24 Zornitza Stark Tag new gene name tag was added to gene: C20orf24.
Mendeliome v1.169 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Mendeliome v1.169 C20orf24 Zornitza Stark gene: C20orf24 was added
gene: C20orf24 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220; 24194475
Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994
Review for gene: C20orf24 was set to RED
Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475.

HGNC approved name is RAB5IF.
Sources: Literature
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094, Susceptibility to mycobacteria and Salmonella Edit
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094
Mendeliome v1.168 IL23R Zornitza Stark Phenotypes for gene: IL23R were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease, MONDO:0021094; Susceptibility to mycobacteria and Salmonella
Mendeliome v1.167 IL23R Zornitza Stark Publications for gene: IL23R were set to 30578351
Mendeliome v1.166 IL23R Zornitza Stark Classified gene: IL23R as Amber List (moderate evidence)
Mendeliome v1.166 IL23R Zornitza Stark Gene: il23r has been classified as Amber List (Moderate Evidence).
Mendeliome v1.165 IL23R Zornitza Stark edited their review of gene: IL23R: Added comment: PMID 35829840: 48yo male with disseminated NTM homozygous (p.R381X) with supportive functional data.; Changed rating: AMBER; Changed publications: 30578351, 35829840
Mendeliome v1.165 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Mendeliome v1.165 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.164 HYOU1 Zornitza Stark edited their review of gene: HYOU1: Added comment: Second individual reported in PMID: 35822684 with severe neutropenia.; Changed rating: AMBER; Changed publications: 27913302, 35822684; Changed phenotypes: Immunodeficiency 59 and hypoglycemia, MIM# 233600
Mendeliome v1.164 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy
Mendeliome v1.163 CHD5 Elena Savva Phenotypes for gene: CHD5 were changed from Intellectual disability; Epilepsy to Parenti-Mignot neurodevelopmental syndrome MIM#619873
Mendeliome v1.162 CHD5 Elena Savva reviewed gene: CHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33944996; Phenotypes: Parenti-Mignot neurodevelopmental syndrome MIM#619873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.162 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.162 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.161 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Mendeliome v1.160 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.159 UBA2 Zornitza Stark reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ACCES syndrome, MIM# 619959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.159 C9orf84 Zornitza Stark Classified gene: C9orf84 as Green List (high evidence)
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.158 C9orf84 Zornitza Stark Tag new gene name tag was added to gene: C9orf84.
Mendeliome v1.158 C9orf84 Zornitza Stark changed review comment from: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature; to: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. A male germ cell-specific Shoc1 knockout mouse model recapitulates the phenotype (germline knockout: early lethality).

HGNC approved name is SHOC1.

Sources: Literature
Mendeliome v1.158 C9orf84 Zornitza Stark gene: C9orf84 was added
gene: C9orf84 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf84 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf84 were set to 32741963; 32900840; 35485979
Phenotypes for gene: C9orf84 were set to Spermatogenic failure 75, MIM# 619949
Review for gene: C9orf84 was set to GREEN
Added comment: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature
Mendeliome v1.157 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Mendeliome v1.156 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Mendeliome v1.156 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.156 KMT2B Zornitza Stark Publications for gene: KMT2B were set to 27839873; 27992417
Mendeliome v1.155 KMT2B Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 27839873, 27992417, 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Mendeliome v1.155 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Changed phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929, Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.154 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929 to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929; Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.153 CDH2 Zornitza Stark Mode of inheritance for gene: CDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.152 CDH2 Zornitza Stark edited their review of gene: CDH2: Added comment: PMID 34702855: three sibs with homozygous missense and strikingly severe ADHD. Mouse model of same variant recapitulated the phenotype. AMBER for bi-allelic association (segregation and functional data).; Changed publications: 31585109, 34702855; Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929:Attention deficit-hyperactivity disorder 8 , MIM# 619957; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.152 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 PLXNA1 Zornitza Stark edited their review of gene: PLXNA1: Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 TBP Zornitza Stark Tag STR tag was added to gene: TBP.
Mendeliome v1.151 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; deafness; heterochromia iridis; hypopigmentation of the skin; hyperpigmentation of the skin; Waardenburg syndrome,MONDO:0018094, KITLG-related
Mendeliome v1.150 KITLG Zornitza Stark Publications for gene: KITLG were set to 26522471
Mendeliome v1.149 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Mendeliome v1.149 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.147 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Mendeliome v1.146 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to 26524591
Mendeliome v1.145 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.144 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Mendeliome v1.144 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Added comment: Two additional individuals with neonatal onset autoinflammatory syndrome and a mouse model. De novo recurrent missense G156D.; Changed rating: GREEN; Changed publications: 26524591, 34819510; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.143 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.142 HCK Zornitza Stark gene: HCK was added
gene: HCK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HCK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCK were set to 34536415
Phenotypes for gene: HCK were set to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Mode of pathogenicity for gene: HCK was set to Other
Review for gene: HCK was set to AMBER
Added comment: Single patient with supportive functional data.
Sources: Literature
Mendeliome v1.141 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Mendeliome v1.141 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.140 TBX21 Zornitza Stark changed review comment from: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified.

Association with asthma and nasal polyps pertains to promoter SNPs.; to: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Functional data.

Association with asthma and nasal polyps pertains to promoter SNPs.
Mendeliome v1.140 TBX21 Zornitza Stark edited their review of gene: TBX21: Changed rating: AMBER
Mendeliome v1.140 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Mendeliome v1.139 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Mendeliome v1.139 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Mendeliome v1.138 KITLG Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome,MONDO:0018094, KITLG-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.138 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Mendeliome v1.138 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Mendeliome v1.137 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Mendeliome v1.135 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Mendeliome v1.135 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.134 PIK3C2B Krithika Murali gene: PIK3C2B was added
gene: PIK3C2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2B were set to PMID:35786744
Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704
Review for gene: PIK3C2B was set to AMBER
Added comment: No OMIM gene disease association.

Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation.
Sources: Literature
Mendeliome v1.134 CCDC155 Zornitza Stark Tag new gene name tag was added to gene: CCDC155.
Mendeliome v1.134 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.133 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Traboulsi syndrome , MIM#601552 to Traboulsi syndrome , MIM#601552; Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Mendeliome v1.132 ASPH Zornitza Stark Publications for gene: ASPH were set to 24768550; 30194805; 34018898
Mendeliome v1.131 ASPH Zornitza Stark Mode of inheritance for gene: ASPH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.130 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Mendeliome v1.130 ASPH Paul De Fazio reviewed gene: ASPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 35697689; Phenotypes: Exertional heat illness, malignant hyperthermia susceptibility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.130 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.128 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.127 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.127 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.126 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Mendeliome v1.126 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging.
Sources: Literature
Mendeliome v1.126 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.126 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.125 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Mendeliome v1.124 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Mendeliome v1.124 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.123 TMEM63C Elena Savva gene: TMEM63C was added
gene: TMEM63C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM63C were set to PMID: 35718349
Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related
Review for gene: TMEM63C was set to GREEN
Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families.
Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development. Single patient was microcephalic
Sources: Literature
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.122 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.121 MAL Zornitza Stark gene: MAL was added
gene: MAL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAL was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Mendeliome v1.120 RELN Zornitza Stark Publications for gene: RELN were set to 32001840
Mendeliome v1.119 RELN Zornitza Stark edited their review of gene: RELN: Added comment: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile. Additional 7 individuals from 4 families with bi-allelic variants.; Changed publications: 35769015
Mendeliome v1.119 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Mendeliome v1.119 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Mendeliome v1.119 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.119 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.118 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Mendeliome. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Mendeliome v1.117 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934) to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934); Spinocerebellar ataxia 25, MIM# 608703
Mendeliome v1.116 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 31752325; 30244537; 28594066; 28645153; 33199448
Mendeliome v1.115 PNPT1 Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.114 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old. Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.; Changed rating: AMBER; Changed publications: 35411967; Changed phenotypes: Spinocerebellar ataxia 25, MIM# 608703; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.114 TTC25 Arina Puzriakova reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.114 CXCR2 Zornitza Stark Classified gene: CXCR2 as Green List (high evidence)
Mendeliome v1.114 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Green List (High Evidence).
Mendeliome v1.113 CXCR2 Zornitza Stark edited their review of gene: CXCR2: Added comment: 4 unrelated patients with neutropaenia reported.; Changed rating: GREEN; Changed publications: 24777453, 34854278; Changed phenotypes: WHIM syndrome 2, MIM#619407
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.113 RHOG Zornitza Stark Classified gene: RHOG as Amber List (moderate evidence)
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.112 RHOG Zornitza Stark gene: RHOG was added
gene: RHOG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHOG were set to 33513601
Phenotypes for gene: RHOG were set to Genetic HLH, MONDO:0015541, RHOG-related
Review for gene: RHOG was set to AMBER
Added comment: Single individual reported, extensive functional data supports gene-disease association.
Sources: Literature
Mendeliome v1.111 TNFSF13 Zornitza Stark Marked gene: TNFSF13 as ready
Mendeliome v1.111 TNFSF13 Zornitza Stark Gene: tnfsf13 has been classified as Red List (Low Evidence).
Mendeliome v1.111 TNFSF13 Zornitza Stark gene: TNFSF13 was added
gene: TNFSF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNFSF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF13 were set to 32298700
Phenotypes for gene: TNFSF13 were set to Hypogammaglobulinaemia, MONDO:0015977, TNSF13-related
Review for gene: TNFSF13 was set to RED
Added comment: Single individual, consanguineous parents.
Sources: Literature
Mendeliome v1.110 POU2AF1 Zornitza Stark Gene: pou2af1 has been classified as Red List (Low Evidence).
Mendeliome v1.110 POU2AF1 Zornitza Stark gene: POU2AF1 was added
gene: POU2AF1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POU2AF1 were set to 33571536
Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related
Review for gene: POU2AF1 was set to RED
Added comment: Single individual from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers.
Sources: Expert Review
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.109 CD28 Zornitza Stark Classified gene: CD28 as Amber List (moderate evidence)
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.108 CD28 Zornitza Stark edited their review of gene: CD28: Changed rating: AMBER
Mendeliome v1.108 CD28 Zornitza Stark changed review comment from: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review; to: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1.
Sources: Expert Review
Mendeliome v1.108 CD28 Zornitza Stark gene: CD28 was added
gene: CD28 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD28 were set to 34214472
Phenotypes for gene: CD28 were set to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs
Review for gene: CD28 was set to RED
Added comment: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review
Mendeliome v1.107 IKZF3 Zornitza Stark Classified gene: IKZF3 as Green List (high evidence)
Mendeliome v1.107 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Mendeliome v1.106 IKZF3 Zornitza Stark edited their review of gene: IKZF3: Added comment: Additional multigenerational family where novel missense variant segregated with disease in 4 individuals.; Changed rating: GREEN; Changed publications: 34155405, 34694366
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.106 COPG1 Zornitza Stark Classified gene: COPG1 as Amber List (moderate evidence)
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.105 COPG1 Zornitza Stark edited their review of gene: COPG1: Changed rating: AMBER
Mendeliome v1.105 COPG1 Zornitza Stark gene: COPG1 was added
gene: COPG1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPG1 were set to 33529166
Phenotypes for gene: COPG1 were set to Combined immunodeficiency MONDO:0015131, COPG1-related
Review for gene: COPG1 was set to RED
Added comment: Five Omani siblings, born to consanguineous parents, homozygous missense.

Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice.
Sources: Expert Review
Mendeliome v1.104 TSPAN7 Zornitza Stark Tag disputed was removed from gene: TSPAN7.
Mendeliome v1.104 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Added comment: Two families reported with LoF variants and ID: Abidi FE et al. 2002 Jun (PMID:12070254); Zemni R et al. 2000 Feb (PMID:10655063)

Assessed as MODERATE by ClinGen.; Changed rating: AMBER; Changed publications: 12070254, 10655063
Mendeliome v1.104 TSPAN7 Zornitza Stark Tag disputed tag was added to gene: TSPAN7.
Mendeliome v1.104 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Changed rating: RED
Mendeliome v1.104 IFNAR2 Zornitza Stark Publications for gene: IFNAR2 were set to 26424569
Mendeliome v1.103 IFNAR2 Zornitza Stark Classified gene: IFNAR2 as Green List (high evidence)
Mendeliome v1.103 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Green List (High Evidence).
Mendeliome v1.102 IFNAR2 Zornitza Stark edited their review of gene: IFNAR2: Added comment: Five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination; Changed rating: GREEN; Changed publications: 26424569, 35442417
Mendeliome v1.102 IFNAR1 Zornitza Stark Phenotypes for gene: IFNAR1 were changed from Severe disease caused by Yellow Fever vaccine and Measles vaccine to Immunodeficiency 106, susceptibility to viral infections, MIM# 619935; Severe disease caused by Yellow Fever vaccine and Measles vaccine
Mendeliome v1.101 IFNAR1 Zornitza Stark Publications for gene: IFNAR1 were set to 31270247
Mendeliome v1.100 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Green List (high evidence)
Mendeliome v1.100 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Green List (High Evidence).
Mendeliome v1.99 IFNAR1 Zornitza Stark edited their review of gene: IFNAR1: Changed rating: GREEN
Mendeliome v1.99 IFNAR1 Zornitza Stark edited their review of gene: IFNAR1: Added comment: Seven children from five unrelated kindreds; Changed publications: 31270247, 35442418; Changed phenotypes: Immunodeficiency 106, susceptibility to viral infections, MIM# 619935, Severe disease caused by Yellow Fever vaccine and Measles vaccine
Mendeliome v1.99 SLC26A1 Zornitza Stark Tag disputed tag was added to gene: SLC26A1.
Mendeliome v1.99 SLC26A1 Zornitza Stark Classified gene: SLC26A1 as Red List (low evidence)
Mendeliome v1.99 SLC26A1 Zornitza Stark Gene: slc26a1 has been classified as Red List (Low Evidence).
Mendeliome v1.98 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174 to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Mendeliome v1.97 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.96 NEK8 Zornitza Stark edited their review of gene: NEK8: Added comment: ESHG 2022: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs) -3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln) -suspected dominant negative effect -patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8 (Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF); Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Familial renal cystic disease MONDO:0019741, NEK8-related, dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.96 DRD2 Zornitza Stark Phenotypes for gene: DRD2 were changed from to Combined dystonia, MONDO:0020065, DRD2-related; dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems
Mendeliome v1.95 DRD2 Zornitza Stark Mode of pathogenicity for gene: DRD2 was changed from to Other
Mendeliome v1.94 DRD2 Zornitza Stark Mode of inheritance for gene: DRD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.93 DRD2 Zornitza Stark reviewed gene: DRD2: Rating: RED; Mode of pathogenicity: Other; Publications: 33200438; Phenotypes: Combined dystonia, MONDO:0020065, DRD2-related, dystonia, chorea, anxiety, ataxia, orofacial dyskinesia, tremor, memory problems; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.93 THSD1 Zornitza Stark Phenotypes for gene: THSD1 were changed from Aneurysm, intracranial berry, 12 , MIM# 618734 to Aneurysm, intracranial berry, 12 , MIM# 618734; Hydrops fetalis MONDO:0015193, THSD1-related
Mendeliome v1.92 THSD1 Zornitza Stark Publications for gene: THSD1 were set to 27895300
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Mendeliome v1.90 TRPM3 Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, TRPM3-related
Mendeliome v1.89 SLC26A1 Krithika Murali reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Nephrolithiasis, calcium oxalate - MIM#167030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.89 DDR2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating.; to: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia. LoF.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating. GoF.
Mendeliome v1.89 TNNT1 Bryony Thompson Phenotypes for gene: TNNT1 were changed from Nemaline myopathy 5, Amish type, MIM# 605355 to Nemaline myopathy 5, Amish type, MIM# 605355; nemaline myopathy MONDO:0018958
Mendeliome v1.88 TNNT1 Bryony Thompson Publications for gene: TNNT1 were set to
Mendeliome v1.87 TNNT1 Bryony Thompson Added comment: Comment on mode of inheritance: There is emerging evidence for monoallelic mode of inheritance
Mendeliome v1.87 TNNT1 Bryony Thompson Mode of inheritance for gene: TNNT1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.86 TNNT1 Bryony Thompson Mode of inheritance for gene: TNNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.85 TNNT1 Bryony Thompson reviewed gene: TNNT1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 29178646, 35510366; Phenotypes: nemaline myopathy MONDO:0018958; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.85 EPHA2 Elena Savva reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34638995, 19005574, 19649315, 19306328, 33671840; Phenotypes: Early-Onset Cataract, cataract 6 multiple types MONDO:0007288; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.85 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927, Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.85 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.84 GRIA1 Zornitza Stark Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Mendeliome v1.83 GRIA1 Zornitza Stark Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.82 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Added comment: Single individual reported with bi-allelic LoF variant. RED/AMBER for bi-allelic variants.; Changed publications: 28628100, 23033978, 26350204, 24896178, 35675825; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.82 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual disability; autism to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Mendeliome v1.81 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Mendeliome v1.81 MSH5 Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442 to Spermatogenic failure 74, MIM# 619937; Premature ovarian failure 13, MIM#617442
Mendeliome v1.80 MSH5 Zornitza Stark reviewed gene: MSH5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 74, MIM# 619937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.80 MSH5 Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13 MIM#617442 to Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442
Mendeliome v1.79 THSD1 Elena Savva reviewed gene: THSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33569873, 27895300; Phenotypes: Aneurysm, intracranial berry, 12 MIM# 618734, nonimmune hydrops fetalis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.79 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230 to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Hereditary spastic paraplegia MONDO:0019064, GCH1-related
Mendeliome v1.78 GCH1 Zornitza Stark Publications for gene: GCH1 were set to 7874165; 11113234; 15753436; 9667588; 10987649; 32170445; 32278297; 32746945; 30314816
Mendeliome v1.77 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21935284, 24509643, 33713342; Phenotypes: Hereditary spastic paraplegia MONDO:0019064, GCH1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.77 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4A, autosomal dominant , MIM#619752, Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant, Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v1.77 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Dystonia 35, childhood-onset , MIM# 619921; Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Mendeliome v1.76 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921, Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Mendeliome v1.76 KCNA5 Zornitza Stark Classified gene: KCNA5 as Amber List (moderate evidence)
Mendeliome v1.76 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.75 KCNA5 Zornitza Stark edited their review of gene: KCNA5: Added comment: Multiple families reported. At least one with LoF variant, rest missense. The missense variants are present in the population, ranging from 2 to 40 individuals in gnomad, which raises doubt about their pathogenicity.; Changed rating: AMBER
Mendeliome v1.75 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Mendeliome v1.74 GATA1 Zornitza Stark Deleted their comment
Mendeliome v1.74 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: Variants in GATA1 are associated with a number of haematological disorders, which probably represent a spectrum rather than distinct entities.; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Mendeliome v1.74 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual disability; epilepsy to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.73 NR4A2 Zornitza Stark edited their review of gene: NR4A2: Changed phenotypes: Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.73 KCNA5 Chern Lim reviewed gene: KCNA5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v1.73 KCNC2 Zornitza Stark Phenotypes for gene: KCNC2 were changed from epileptic encephalopathy; spastic tetraplegia; opisthotonos attacks; intellectual disability; West syndrome to Developmental and epileptic encephalopathy 103, MIM# 619913
Mendeliome v1.72 KCNC2 Zornitza Stark Publications for gene: KCNC2 were set to 32392612; 31972370
Mendeliome v1.71 KCNC2 Zornitza Stark Classified gene: KCNC2 as Green List (high evidence)
Mendeliome v1.71 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Mendeliome v1.70 KCNC2 Zornitza Stark reviewed gene: KCNC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314505; Phenotypes: Developmental and epileptic encephalopathy 103, MIM# 619913; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.70 KCNJ1 Zornitza Stark Publications for gene: KCNJ1 were set to 28630040
Mendeliome v1.69 KCNJ1 Zornitza Stark reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841184, 19096086, 7635463, 12086641, 9580661, 12122007; Phenotypes: Bartter syndrome, type 2, MIM#241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.69 ATP2B1 Zornitza Stark Phenotypes for gene: ATP2B1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related to Intellectual developmental disorder, autosomal dominant 66, MIM# 619910
Mendeliome v1.68 ATP2B1 Zornitza Stark reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 66, MIM# 619910; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.68 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976
Mendeliome v1.67 PRDM13 Zornitza Stark Publications for gene: PRDM13 were set to 30710461; 34730112; 35390279
Mendeliome v1.66 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976 -- this likely lies on the same spectrum as Pontocerebellar hypoplasia, type 17, MIM# 619909 rather than being a distinct disorder.; Changed publications: 30710461, 34730112; Changed phenotypes: Retinal dystrophy, Chorioretinal atrophy, progressive bifocal, MIM# 600790, Pontocerebellar hypoplasia, type 17, MIM# 619909, Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.66 TIAM1 Zornitza Stark Phenotypes for gene: TIAM1 were changed from Neurodevelopmental disorder, TIAM1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and seizures, MIM# 619908
Mendeliome v1.65 RBFOX2 Chern Lim changed review comment from: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; to: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Mendeliome v1.65 CSNK2B Bryony Thompson Phenotypes for gene: CSNK2B were changed from Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732 to Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732; Craniodigital syndrome-intellectual disability syndrome MONDO:0015463
Mendeliome v1.64 CSNK2B Bryony Thompson Publications for gene: CSNK2B were set to 28585349; 28762608
Mendeliome v1.63 CSNK2B Bryony Thompson reviewed gene: CSNK2B: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35571680; Phenotypes: Craniodigital syndrome-intellectual disability syndrome MONDO:0015463; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.63 SLC5A6 Zornitza Stark Phenotypes for gene: SLC5A6 were changed from Developmental delay; epilepsy; neurodegeneration; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973 to Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Mendeliome v1.62 SLC5A6 Zornitza Stark Publications for gene: SLC5A6 were set to 31754459; 27904971
Mendeliome v1.61 SLC5A6 Zornitza Stark changed review comment from: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature; to: Complex neurodegenerative disorder: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature
Mendeliome v1.61 SLC5A6 Zornitza Stark edited their review of gene: SLC5A6: Added comment: PMID 35013551: 5 individuals from 3 unrelated families reported with predominantly neuropathy phenotype.; Changed publications: 31754459, 27904971, 35013551; Changed phenotypes: Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903, Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Mendeliome v1.61 SASH3 Zornitza Stark Phenotypes for gene: SASH3 were changed from Combined immunodeficiency; immune dysregulation to Immunodeficiency 102, MIM# 301082
Mendeliome v1.60 SASH3 Zornitza Stark edited their review of gene: SASH3: Changed phenotypes: Immunodeficiency 102, MIM# 301082
Mendeliome v1.60 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.60 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.59 BUB1 Zornitza Stark reviewed gene: BUB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.59 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.59 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.58 IREB2 Zornitza Stark Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Mendeliome v1.57 GIMAP6 Zornitza Stark Phenotypes for gene: GIMAP6 were changed from Autophagy, immune competence and inflammation to Autoinflammatory syndrome MONDO:0019751, GIMAP6-related
Mendeliome v1.56 GIMAP6 Zornitza Stark reviewed gene: GIMAP6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome MONDO:0019751, GIMAP6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.56 BUB1 Elena Savva Classified gene: BUB1 as Red List (low evidence)
Mendeliome v1.56 BUB1 Elena Savva Gene: bub1 has been classified as Red List (Low Evidence).
Mendeliome v1.55 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Neurodevelopmental disorder, MONDO:0700092, PAN2-related to Syndromic disease MONDO:0002254, PAN2-related
Mendeliome v1.54 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.54 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from Retinitis pigmentosa 13, MIM#600059 to Retinitis pigmentosa 13, MIM#600059; Neurodevelopmental disorder MONDO:0700092, PRPF8-related
Mendeliome v1.53 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.53 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Classified gene: RRM1 as Amber List (moderate evidence)
Mendeliome v1.52 RRM1 Seb Lunke Added comment: Comment on list classification: 3 families but only 2 Hom variants, not convinced they are definitely unrelated. 4th probed inconclusive.
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 BUB1 Zornitza Stark Phenotypes for gene: BUB1 were changed from Intellectual disability and microcephaly to Neurodevelopmental disorder, BUB1-related MONDO:0700092
Mendeliome v1.51 BUB1 Zornitza Stark Classified gene: BUB1 as Green List (high evidence)
Mendeliome v1.51 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.50 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.49 RRM1 Daniel Flanagan gene: RRM1 was added
gene: RRM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM1 were set to 35617047
Phenotypes for gene: RRM1 were set to Multiple mitochondrial DNA deletion syndrome (MONDO:0016797)
Review for gene: RRM1 was set to GREEN
Added comment: Homozygous missense were identified in 4 four probands (p.Arg381Cys or p.Arg381His) from three families, who presented with ptosis and ophthalmoplegia, plus other manifestations and multiple mtDNA deletions in muscle. Heterozygous carriers were unaffected. An additional proband was heterozygous for a different RRM1 missense (p.Asn427Lys), another variant not identified.
Sources: Expert list
Mendeliome v1.49 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Mendeliome v1.49 LMOD2 Seb Lunke Phenotypes for gene: LMOD2 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Mendeliome v1.48 ATOH1 Zornitza Stark Marked gene: ATOH1 as ready
Mendeliome v1.48 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.48 LMOD2 Seb Lunke Classified gene: LMOD2 as Green List (high evidence)
Mendeliome v1.48 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Mendeliome v1.47 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Neurodevelopmental disorder, MONDO:0700092, PAN2-related
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Mendeliome v1.47 PRPF8 Krithika Murali reviewed gene: PRPF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35543142; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.47 ATOH1 Zornitza Stark Phenotypes for gene: ATOH1 were changed from Pontocerebellar hypoplasia; developmental delay; hearing loss to Pontocerebellar hypoplasia MONDO:0020135, ATOH1-related
Mendeliome v1.46 ATOH1 Zornitza Stark Classified gene: ATOH1 as Amber List (moderate evidence)
Mendeliome v1.46 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Marked gene: PTPN13 as ready
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Classified gene: PTPN13 as Amber List (moderate evidence)
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.45 PTPN13 Ain Roesley gene: PTPN13 was added
gene: PTPN13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN13 were set to 35643866
Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related
Review for gene: PTPN13 was set to AMBER
gene: PTPN13 was marked as current diagnostic
Added comment: 2 families

Family A: 3 affecteds only 2 sequenced. Hom for a missense
3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia
noted that the sibling who wasn't sequenced had normal bone marrow morphology

Family B: Chet for a missense and inframe del of 1 amino acid
Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement

In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A
Sources: Literature
Mendeliome v1.44 BUB1 Paul De Fazio edited their review of gene: BUB1: Changed phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092, Intellectual disability and microcephaly
Mendeliome v1.44 ATOH1 Chloe Stutterd gene: ATOH1 was added
gene: ATOH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATOH1 were set to 35518571
Phenotypes for gene: ATOH1 were set to Pontocerebellar hypoplasia; developmental delay; hearing loss
Penetrance for gene: ATOH1 were set to unknown
Review for gene: ATOH1 was set to AMBER
Added comment: Single report of novel homozygous missense variant in functional domain segregating with disease in two affected siblings with pontocerebellar hypoplasia, developmental delay and hearing loss. Similar phenotype previously reported in animal model with biallelic missense variant affecting same functional domain. Homology modelling predicts this missense variant affects binding capability of the bHLH domain to the DNA. Gene encodes a core transcription factor in developing cerebellum, brainstem, dorsal spinal cord and ear.
Sources: Literature
Mendeliome v1.44 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly
Review for gene: BUB1 was set to GREEN
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Mendeliome v1.44 LMOD2 Melanie Marty gene: LMOD2 was added
gene: LMOD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LMOD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD2 were set to PMID: 31517052; PMID: 34888509; PMID: 35082396; PMID: 35188328; PMID: 26487682
Phenotypes for gene: LMOD2 were set to Dilated cardiomyopathy
Review for gene: LMOD2 was set to GREEN
Added comment: 4 unrelated families with early onset dilated cardiomyopathy, autosomal recessive inheritance, functional studies showing loss of protein and a mouse model reported.

PMID: 31517052 1 x neonate with DCM, homozygous nonsense variant identified.

PMID: 34888509 2 x neonatal deaths (from 1 family) related to dilated cardiomyopathy (DCM), compound heterozygous loss-of-function variants identified.

PMID:35082396 2 x siblings with DCM who died shortly after birth due to heart failure, homozygous canonical splice variant identified. Functional studies show loss of donor site and loss of protein.

PMID: 35188328 1 x child (9 months) with DCM, with homozygous frameshift variant. Functional studies showed absence of LMOD2 protein (western blot).

PMID: 26487682 Lmod2 null (knockout) mice present with short cardiac thin filaments and die at ~3 weeks due to dysfunctional, dilated hearts
Sources: Literature
Mendeliome v1.44 SEMA6B Zornitza Stark Phenotypes for gene: SEMA6B were changed from Progressive myoclonic epilepsy to Progressive myoclonic epilepsy; Intellectual disability, MONDO:0001071, SEMA6B related
Mendeliome v1.43 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from Developmental disorders to Neurodevelopmental disorder MONDO:0700092 SRRM2-related
Mendeliome v1.42 SEMA6B Zornitza Stark Publications for gene: SEMA6B were set to 32169168
Mendeliome v1.41 SEMA6B Dean Phelan Deleted their comment
Mendeliome v1.41 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Mendeliome v1.41 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Mendeliome v1.40 SEMA6B Dean Phelan commented on gene: SEMA6B: PMID: 35604360
- 14 heterozygous variants were observed in 16 unrelated individuals referred for intellectual disability. Majority of the variants 9/14 were PTCs in the last exon and predicted to escape NMD. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Mendeliome v1.40 SEMA6B Dean Phelan reviewed gene: SEMA6B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35604360; Phenotypes: Intellectual disability, MONDO:0001071, SEMA6B related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.40 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.39 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related to Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related
Mendeliome v1.38 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Mendeliome v1.38 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.38 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from DiMONDO:0015253 to Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related
Mendeliome v1.37 IREB2 Lucy Spencer reviewed gene: IREB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35602653; Phenotypes: Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.37 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability to DiMONDO:0015253
Mendeliome v1.36 SRRM2 Michelle Torres reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35567594; Phenotypes: neurodevelopmental disorder MONDO:0700092 SRRM2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.36 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Mendeliome v1.36 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.35 GIMAP6 Elena Savva gene: GIMAP6 was added
gene: GIMAP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581
Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation
Review for gene: GIMAP6 was set to AMBER
Added comment: PMID: 35551368, PMID: 33328581
- K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency.
- 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous.
Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions.
Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly.
Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections

- Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux).

gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript
Sources: Literature
Mendeliome v1.34 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Mendeliome v1.34 TRIM47 Zornitza Stark Marked gene: TRIM47 as ready
Mendeliome v1.34 TRIM47 Zornitza Stark Gene: trim47 has been classified as Red List (Low Evidence).
Mendeliome v1.34 TRIM47 Zornitza Stark gene: TRIM47 was added
gene: TRIM47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM47 were set to 35511193
Phenotypes for gene: TRIM47 were set to Genetic cerebral small vessel disease MONDO:0018787
Review for gene: TRIM47 was set to RED
Added comment: GWAS data: Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. Observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology.
Sources: Literature
Mendeliome v1.33 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Mendeliome v1.32 HIST1H4J Zornitza Stark Phenotypes for gene: HIST1H4J were changed from microcephaly; intellectual disability; dysmorphic features to Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759
Mendeliome v1.31 HIST1H4J Zornitza Stark edited their review of gene: HIST1H4J: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759
Mendeliome v1.31 MESP1 Zornitza Stark Phenotypes for gene: MESP1 were changed from Congenital heart disease to Congenital heart disease MONDO:0005453
Mendeliome v1.30 DNM2 Zornitza Stark Mode of inheritance for gene: DNM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.29 SPTAN1 Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5, MIM# 613477; hereditary motor neuropathy to Developmental and epileptic encephalopathy 5, MIM# 613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; hereditary motor neuropathy
Mendeliome v1.28 SPTAN1 Zornitza Stark edited their review of gene: SPTAN1: Added comment: Leveille et al (2019) - 2 patients with HSP with biallelic missense SPTAN1 variants Previously described zebrafish, mouse, and rat animal models of SPTAN1 deficiency, all consistently showing axonal degeneration, fitting the pathological features of HSP in humans. Xie et al (2022) - 1 patient with complicated HSP and homozygous SPTAN1 mutation. Healthy parents and sister all carried the heterozygous mutation. Van de Vondel et al (2022) - 22 patients from 14 families with five novel heterozygous SPTAN1 variants. Presentations ranged from cerebellar ataxia, intellectual disability, epilepsy, and spastic paraplegia. A recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia. Through protein modeling they showed that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat.; Changed publications: 20493457, 22258530, 32811770, 35150594, 34526651, 31515523; Changed phenotypes: Developmental and epileptic encephalopathy 5, MIM# 613477, Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.28 U2AF2 Zornitza Stark Phenotypes for gene: U2AF2 were changed from Developmental disorders to Neurodevelopmental disorder MONDO:0700092, U2AF2-related
Mendeliome v1.27 MMGT1 Zornitza Stark Phenotypes for gene: MMGT1 were changed from Developmental disorders to Neurodevelopmental disorder MONDO:0700092, MMGT1-related
Mendeliome v1.26 MSX1 Zornitza Stark Publications for gene: MSX1 were set to 33419968, 33708320, 32192766
Mendeliome v1.25 LRP2 Zornitza Stark Publications for gene: LRP2 were set to
Mendeliome v1.24 LRP2 Zornitza Stark Mode of inheritance for gene: LRP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.23 AURKC Zornitza Stark Publications for gene: AURKC were set to
Mendeliome v1.22 AURKC Zornitza Stark Classified gene: AURKC as Green List (high evidence)
Mendeliome v1.22 AURKC Zornitza Stark Gene: aurkc has been classified as Green List (High Evidence).
Mendeliome v1.21 AURKC Zornitza Stark reviewed gene: AURKC: Rating: GREEN; Mode of pathogenicity: None; Publications: 21733974, 19147683; Phenotypes: Spermatogenic failure 5 , OMIM #243060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.21 GJA5 Zornitza Stark Classified gene: GJA5 as Amber List (moderate evidence)
Mendeliome v1.21 GJA5 Zornitza Stark Gene: gja5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.20 GJA5 Zornitza Stark reviewed gene: GJA5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial fibrillation, familial, 11, OMIM# 614049; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.20 GINS1 Zornitza Stark Phenotypes for gene: GINS1 were changed from to Immunodeficiency 55, OMIM #617827
Mendeliome v1.19 ATG16L1 Zornitza Stark reviewed gene: ATG16L1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.19 PLCH1 Zornitza Stark Phenotypes for gene: PLCH1 were changed from Holoprosencephaly spectrum; Severe developmental delay; Brain malformations to Holoprosencephaly 14, MIM# 619895
Mendeliome v1.18 PLCH1 Zornitza Stark reviewed gene: PLCH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 14, MIM# 619895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.18 TULP3 Zornitza Stark Phenotypes for gene: TULP3 were changed from progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 to Hepatorenocardiac degenerative fibrosis, MIM# 619902
Mendeliome v1.17 TULP3 Zornitza Stark reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM# 619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.17 IKBKG Zornitza Stark edited their review of gene: IKBKG: Changed publications: 31874111, 35289316
Mendeliome v1.17 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Mendeliome v1.16 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300 to Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300; Autoinflammatory disease, systemic, X-linked, MIM# 301081
Mendeliome v1.15 IKBKG Zornitza Stark edited their review of gene: IKBKG: Added comment: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5).

Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; Changed phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081
Mendeliome v1.15 MYO9A Zornitza Stark Classified gene: MYO9A as Amber List (moderate evidence)
Mendeliome v1.15 MYO9A Zornitza Stark Gene: myo9a has been classified as Amber List (Moderate Evidence).
Mendeliome v1.14 MYO9A Zornitza Stark edited their review of gene: MYO9A: Added comment: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.; Changed rating: AMBER
Mendeliome v1.14 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related to Developmental and epileptic encephalopathy 102, MIM# 619881
Mendeliome v1.13 SLC38A3 Zornitza Stark reviewed gene: SLC38A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 102, MIM# 619881; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.13 FAT2 Elena Savva Publications for gene: FAT2 were set to 29053796
Mendeliome v1.13 FAT2 Elena Savva Classified gene: FAT2 as Green List (high evidence)
Mendeliome v1.13 FAT2 Elena Savva Gene: fat2 has been classified as Green List (High Evidence).
Mendeliome v1.12 FAT2 Elena Savva reviewed gene: FAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33884300, 29053796; Phenotypes: Spinocerebellar ataxia 45, MIM#617769; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.12 GFRA1 Zornitza Stark Phenotypes for gene: GFRA1 were changed from Renal agenesis to Renal hypodysplasia/aplasia 4, MIM# 619887
Mendeliome v1.11 GFRA1 Zornitza Stark edited their review of gene: GFRA1: Changed phenotypes: Renal hypodysplasia/aplasia 4, MIM# 619887
Mendeliome v1.11 COPB2 Zornitza Stark Phenotypes for gene: COPB2 were changed from Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis and developmental delay to Microcephaly 19, primary, autosomal recessive, MIM# 617800; Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM# 619884
Mendeliome v1.10 ATP13A3 Zornitza Stark Phenotypes for gene: ATP13A3 were changed from Pulmonary arterial hypertension to Primary pulmonary hypertension 5, MIM#265400
Mendeliome v1.9 ATP13A3 Zornitza Stark edited their review of gene: ATP13A3: Changed phenotypes: Primary pulmonary hypertension 5, MIM#265400
Mendeliome v1.9 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.9 RBFOX2 Zornitza Stark Phenotypes for gene: RBFOX2 were changed from Hypoplastic left heart syndrome (HLHS) to Hypoplastic left heart syndrome (HLHS) MONDO:0004933
Mendeliome v1.8 RBFOX2 Zornitza Stark Classified gene: RBFOX2 as Amber List (moderate evidence)
Mendeliome v1.8 RBFOX2 Zornitza Stark Gene: rbfox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.7 PROSER1 Zornitza Stark Gene: proser1 has been classified as Red List (Low Evidence).
Mendeliome v1.7 PROSER1 Zornitza Stark gene: PROSER1 was added
gene: PROSER1 was added to Mendeliome. Sources: Expert Review
founder tags were added to gene: PROSER1.
Mode of inheritance for gene: PROSER1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROSER1 were set to 35229282
Phenotypes for gene: PROSER1 were set to Syndromic disease MONDO:0002254, PROSER1-related
Review for gene: PROSER1 was set to RED
Added comment: 4 children from 3 related families with developmental delay, hypotonia, seizures, failure-to-thrive, strabismus, drooling, recurrent otitis media, hearing impairment, genitourinary malformations, and common facial features (arched eyebrows, prominent eyes, broad nasal bridge, low-hanging columella, open mouth, thick lower lip, protruding tongue, large low-set ears, and parietal bossing). WES revealed a homozygous frame-shift variant (p.Thr612Glnfs*22) in PROSER1. This encodes the proline and serine rich protein 1, part of the histone methyltransferases KMT2C/KMT2D complexes. PROSER1 stabilizes TET2, a member of the TET family of DNA demethylases which is involved in recruiting the enhancer-associated KMT2C/KMT2D complexes and mediating DNA demethylation, activating gene expression. Therefore, PROSER1 may play vital and potentially general roles in gene regulation. No functional assays and 3 related families, likely founder effect.
Sources: Expert Review
Mendeliome v1.6 SPATA22 Zornitza Stark Marked gene: SPATA22 as ready
Mendeliome v1.6 SPATA22 Zornitza Stark Gene: spata22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.6 SPATA22 Zornitza Stark Classified gene: SPATA22 as Amber List (moderate evidence)
Mendeliome v1.6 SPATA22 Zornitza Stark Gene: spata22 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.5 SPATA22 Zornitza Stark gene: SPATA22 was added
gene: SPATA22 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SPATA22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA22 were set to 35285020
Phenotypes for gene: SPATA22 were set to Premature ovarian insufficiency and nonobstructive azoospermia; Genetic infertility MONDO:0017143
Review for gene: SPATA22 was set to AMBER
Added comment: 1 consanguineous family with two premature ovarian insufficiency (POI) and two nonobstructive azoospermia (NOA) patients. WES identified a homozygous variant in SPATA22 (c.400C>T:p.R134X). Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene-like stage in the proband with NOA. 2nd patient found with idiopathic POI and compound heterozygous variants in SPATA22 (c.900+1G>A and c.31C>T:p.R11X).
Sources: Expert Review
Mendeliome v1.4 RDH11 Zornitza Stark Classified gene: RDH11 as Amber List (moderate evidence)
Mendeliome v1.4 RDH11 Zornitza Stark Gene: rdh11 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.3 RDH11 Zornitza Stark edited their review of gene: RDH11: Added comment: 2nd case reported: 1 Chinese patient with retinitis pigmentosa, juvenile cataracts, intellectual disability, and myopathy. Trio-based WES and whole genomic CNV detection found compound heterozygous variants in RDH11 (p.Leu313Pro and c.75-3C>A) with biparental inheritance. Variant c.75-3C>A was confirmed to be a splice-site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). They found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. Retinol dehydrogenase 11 (RDH11) is an 11-cis-retinol dehydrogenase that has a well-characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very rare, and only one affected family with eye and intelligence involvement has been reported.; Changed rating: AMBER; Changed publications: 24916380, 15634683, 30731079, 18326732, 34988992
Mendeliome v1.3 ETV2 Ain Roesley changed review comment from: 1 family with 4 fetus-es, cHet for a fs (NMD-predicted) and a missense

3/4 vertebral malformations
2/4 Tetralogy of Fallot
1/4 arterial septal defect
1/4 ventricular septal defect, aortic dilatation
1/4 pre-axial polydactyly
Sources: Literature; to: 1 family with 4 fetus-es all cHet for a fs (NMD-predicted) and a missense

3/4 vertebral malformations
2/4 Tetralogy of Fallot
1/4 arterial septal defect
1/4 ventricular septal defect, aortic dilatation
1/4 pre-axial polydactyly
Sources: Literature
Mendeliome v1.3 PCDHGC4 Zornitza Stark Phenotypes for gene: PCDHGC4 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder with poor growth and skeletal anomalies, MIM# 619880
Mendeliome v1.2 PCDHGC4 Zornitza Stark edited their review of gene: PCDHGC4: Changed phenotypes: Neurodevelopmental disorder with poor growth and skeletal anomalies, MIM# 619880
Mendeliome v1.2 ZNF526 Zornitza Stark Phenotypes for gene: ZNF526 were changed from Intellectual disability; Microcephaly; Cataracts; Epilepsy; Hypertonia; Dystonia to Dentici-Novelli neurodevelopmental syndrome, MIM# 619877
Mendeliome v1.1 POLR3F Zornitza Stark Phenotypes for gene: POLR3F were changed from Severe VZV infection to Immunodeficiency 101 (varicella zoster virus-specific), MIM# 619872
Mendeliome v1.0 POLR3F Zornitza Stark edited their review of gene: POLR3F: Changed phenotypes: Immunodeficiency 101 (varicella zoster virus-specific), MIM# 619872
Mendeliome v1.0 Zornitza Stark promoted panel to version 1.0
Mendeliome v0.14798 GLRX3 Zornitza Stark Gene: glrx3 has been classified as Red List (Low Evidence).
Mendeliome v0.14798 GLRX3 Zornitza Stark Publications for gene: GLRX3 were set to
Mendeliome v0.14797 DNM1L Zornitza Stark Gene: dnm1l has been classified as Green List (High Evidence).
Mendeliome v0.14797 DNM1L Zornitza Stark Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR); Optic atrophy 5 - MIM#610708 (AD)
Mendeliome v0.14796 DNM1L Zornitza Stark Mode of inheritance for gene: DNM1L was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14795 DNASE1L3 Zornitza Stark Gene: dnase1l3 has been classified as Green List (High Evidence).
Mendeliome v0.14795 DNASE1L3 Zornitza Stark Phenotypes for gene: DNASE1L3 were changed from to Systemic lupus erythematosus 16 - MIM#614420
Mendeliome v0.14794 DNASE1 Zornitza Stark Gene: dnase1 has been classified as Red List (Low Evidence).
Mendeliome v0.14794 DNASE1L3 Zornitza Stark Publications for gene: DNASE1L3 were set to
Mendeliome v0.14793 DNASE1L3 Zornitza Stark Mode of inheritance for gene: DNASE1L3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14792 DNASE1 Zornitza Stark Phenotypes for gene: DNASE1 were changed from to {Systemic lupus erythematosus, susceptibility to} - MIM#152700
Mendeliome v0.14791 DNAJC6 Zornitza Stark Gene: dnajc6 has been classified as Green List (High Evidence).
Mendeliome v0.14791 DNAJC6 Zornitza Stark Phenotypes for gene: DNAJC6 were changed from to Parkinson disease 19a, juvenile-onset - MIM#615528; Parkinson disease 19b, early-onset - MIM#615528
Mendeliome v0.14790 DNASE1 Zornitza Stark Mode of inheritance for gene: DNASE1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14789 DNAJC6 Zornitza Stark Publications for gene: DNAJC6 were set to
Mendeliome v0.14788 DNASE1 Zornitza Stark Classified gene: DNASE1 as Red List (low evidence)
Mendeliome v0.14788 DNASE1 Zornitza Stark Gene: dnase1 has been classified as Red List (Low Evidence).
Mendeliome v0.14787 DNAJC6 Zornitza Stark Mode of inheritance for gene: DNAJC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14786 DNAJC5 Zornitza Stark Gene: dnajc5 has been classified as Green List (High Evidence).
Mendeliome v0.14786 DNAJC5 Zornitza Stark Phenotypes for gene: DNAJC5 were changed from to Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant - MIM#162350; ceroid lipofuscinosis, neuronal, 4 (Kufs type) - MONDO:0008083
Mendeliome v0.14785 DNAJC5 Zornitza Stark Publications for gene: DNAJC5 were set to
Mendeliome v0.14784 DNAJC3 Zornitza Stark Gene: dnajc3 has been classified as Green List (High Evidence).
Mendeliome v0.14784 DNAJC3 Zornitza Stark Phenotypes for gene: DNAJC3 were changed from to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus - MIM#616192
Mendeliome v0.14783 DNAJC5 Zornitza Stark Mode of inheritance for gene: DNAJC5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14783 DNAJC3 Zornitza Stark Publications for gene: DNAJC3 were set to
Mendeliome v0.14782 DNAJC3 Zornitza Stark Mode of inheritance for gene: DNAJC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14781 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Mendeliome v0.14781 DNAJC21 Zornitza Stark Phenotypes for gene: DNAJC21 were changed from to Bone marrow failure syndrome 3 - MIM#617052
Mendeliome v0.14780 DNAJC21 Zornitza Stark Publications for gene: DNAJC21 were set to
Mendeliome v0.14779 DNM2 Zornitza Stark Gene: dnm2 has been classified as Green List (High Evidence).
Mendeliome v0.14779 DNM2 Zornitza Stark Phenotypes for gene: DNM2 were changed from to Charcot-Marie-Tooth disease, axonal type 2M, MIM# 606482; Charcot-Marie-Tooth disease, dominant intermediate B, MIM# 606482; MONDO:0011674
Mendeliome v0.14778 DNM2 Zornitza Stark Publications for gene: DNM2 were set to
Mendeliome v0.14777 DNM2 Zornitza Stark Mode of inheritance for gene: DNM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14776 DNAJC21 Zornitza Stark Mode of inheritance for gene: DNAJC21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14775 DPY19L2 Zornitza Stark Gene: dpy19l2 has been classified as Green List (High Evidence).
Mendeliome v0.14775 DPY19L2 Zornitza Stark Phenotypes for gene: DPY19L2 were changed from to Spermatogenic failure 9 - MIM#613958
Mendeliome v0.14774 AVPR2 Zornitza Stark Gene: avpr2 has been classified as Green List (High Evidence).
Mendeliome v0.14774 DPY19L2 Zornitza Stark Mode of inheritance for gene: DPY19L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14773 AVP Zornitza Stark Gene: avp has been classified as Green List (High Evidence).
Mendeliome v0.14773 AVP Zornitza Stark Phenotypes for gene: AVP were changed from to Diabetes insipidus, neurohypophyseal MIM#125700
Mendeliome v0.14772 DRAM2 Zornitza Stark Gene: dram2 has been classified as Green List (High Evidence).
Mendeliome v0.14772 DRAM2 Zornitza Stark Phenotypes for gene: DRAM2 were changed from to Cone-rod dystrophy 21 - MIM#616502
Mendeliome v0.14771 AVP Zornitza Stark Publications for gene: AVP were set to
Mendeliome v0.14770 DRAM2 Zornitza Stark Publications for gene: DRAM2 were set to
Mendeliome v0.14769 DRAM2 Zornitza Stark Mode of inheritance for gene: DRAM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14768 AVP Zornitza Stark Mode of inheritance for gene: AVP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14767 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Mendeliome v0.14767 ATP6V1E1 Zornitza Stark Marked gene: ATP6V1E1 as ready
Mendeliome v0.14767 ATP6V1E1 Zornitza Stark Gene: atp6v1e1 has been classified as Green List (High Evidence).
Mendeliome v0.14767 ATP6V1E1 Zornitza Stark Phenotypes for gene: ATP6V1E1 were changed from to Cutis laxa, autosomal recessive, type IIC MIM#617402
Mendeliome v0.14766 ATP6V1E1 Zornitza Stark Publications for gene: ATP6V1E1 were set to
Mendeliome v0.14765 DRD2 Zornitza Stark Classified gene: DRD2 as Red List (low evidence)
Mendeliome v0.14765 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Mendeliome v0.14764 DRD3 Zornitza Stark Gene: drd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14764 ATP6V1E1 Zornitza Stark Mode of inheritance for gene: ATP6V1E1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14763 DRD3 Zornitza Stark Phenotypes for gene: DRD3 were changed from to {Essential tremor, hereditary, 1} - MIM#190300; {Schizophrenia, susceptibility to} - MIM#181500
Mendeliome v0.14762 DRD3 Zornitza Stark Mode of inheritance for gene: DRD3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14761 DRD3 Zornitza Stark Classified gene: DRD3 as Red List (low evidence)
Mendeliome v0.14761 DRD3 Zornitza Stark Gene: drd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14760 ATP2A1 Zornitza Stark Marked gene: ATP2A1 as ready
Mendeliome v0.14760 ATP2A1 Zornitza Stark Gene: atp2a1 has been classified as Green List (High Evidence).
Mendeliome v0.14760 ATP2A1 Zornitza Stark Phenotypes for gene: ATP2A1 were changed from to Brody myopathy, OMIM # 601003
Mendeliome v0.14759 ATP2A1 Zornitza Stark Publications for gene: ATP2A1 were set to
Mendeliome v0.14758 DSC3 Zornitza Stark Gene: dsc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14758 DSC3 Zornitza Stark Phenotypes for gene: DSC3 were changed from to Hypotrichosis and recurrent skin vesicles MIM#613102
Mendeliome v0.14757 ATP2A1 Zornitza Stark Mode of inheritance for gene: ATP2A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14756 DSC3 Zornitza Stark Publications for gene: DSC3 were set to
Mendeliome v0.14755 ADD1 Zornitza Stark Gene: add1 has been classified as Green List (High Evidence).
Mendeliome v0.14755 DSC3 Zornitza Stark Mode of inheritance for gene: DSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14755 ADD1 Zornitza Stark Phenotypes for gene: ADD1 were changed from Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM # to Neurodevelopmental disorder MONDO:0700092, ADD1-related
Mendeliome v0.14754 DSC3 Zornitza Stark Classified gene: DSC3 as Amber List (moderate evidence)
Mendeliome v0.14754 DSC3 Zornitza Stark Gene: dsc3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14753 DSCAM Zornitza Stark Gene: dscam has been classified as Green List (High Evidence).
Mendeliome v0.14753 DSCAM Zornitza Stark Phenotypes for gene: DSCAM were changed from to Autism MONDO:0005260
Mendeliome v0.14752 DSCAM Zornitza Stark Publications for gene: DSCAM were set to
Mendeliome v0.14751 DSCAM Zornitza Stark Classified gene: DSCAM as Green List (high evidence)
Mendeliome v0.14751 DSCAM Zornitza Stark Gene: dscam has been classified as Green List (High Evidence).
Mendeliome v0.14750 DSCAM Zornitza Stark Mode of inheritance for gene: DSCAM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14749 DSCAM Zornitza Stark Classified gene: DSCAM as Amber List (moderate evidence)
Mendeliome v0.14749 DSCAM Zornitza Stark Gene: dscam has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14748 DSE Zornitza Stark Gene: dse has been classified as Green List (High Evidence).
Mendeliome v0.14748 DSE Zornitza Stark Phenotypes for gene: DSE were changed from to Ehlers-Danlos syndrome, musculocontractural type 2 - MIM#615539
Mendeliome v0.14747 DSE Zornitza Stark Publications for gene: DSE were set to
Mendeliome v0.14746 DSE Zornitza Stark Mode of inheritance for gene: DSE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14745 DSG4 Zornitza Stark Gene: dsg4 has been classified as Green List (High Evidence).
Mendeliome v0.14745 DSG4 Zornitza Stark Phenotypes for gene: DSG4 were changed from to Hypotrichosis 6 - MIM#607903
Mendeliome v0.14744 DSG4 Zornitza Stark Publications for gene: DSG4 were set to
Mendeliome v0.14743 DSG4 Zornitza Stark Mode of inheritance for gene: DSG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14742 DSPP Zornitza Stark Gene: dspp has been classified as Green List (High Evidence).
Mendeliome v0.14742 DSPP Zornitza Stark Phenotypes for gene: DSPP were changed from to Deafness, autosomal dominant 39, with dentinogenesis - MIM#605594; Dentin dysplasia, type II - MIM#125420; Dentinogenesis imperfecta, Shields type II - MIM#125490; Dentinogenesis imperfecta, Shields type III - MIM#125500
Mendeliome v0.14741 DSPP Zornitza Stark Mode of inheritance for gene: DSPP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14740 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Mendeliome v0.14740 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from to Thyroid dyshormonogenesis 6 - MIM#607200
Mendeliome v0.14739 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14738 GDNF Elena Savva Gene: gdnf has been classified as Red List (Low Evidence).
Mendeliome v0.14738 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Green List (High Evidence).
Mendeliome v0.14738 DUOXA2 Zornitza Stark Phenotypes for gene: DUOXA2 were changed from to Thyroid dyshormonogenesis 5 - MIM#274900
Mendeliome v0.14737 DUOXA2 Zornitza Stark Mode of inheritance for gene: DUOXA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14736 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPOR Zornitza Stark Gene: epor has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPRS Zornitza Stark Gene: eprs has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPS8 Zornitza Stark Gene: eps8 has been classified as Green List (High Evidence).
Mendeliome v0.14736 EPS8 Zornitza Stark Phenotypes for gene: EPS8 were changed from to Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428
Mendeliome v0.14735 EPS8 Zornitza Stark Publications for gene: EPS8 were set to
Mendeliome v0.14734 EPS8 Zornitza Stark Mode of inheritance for gene: EPS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14733 ETFB Zornitza Stark Marked gene: ETFB as ready
Mendeliome v0.14733 ETFB Zornitza Stark Gene: etfb has been classified as Green List (High Evidence).
Mendeliome v0.14733 ETFB Zornitza Stark Phenotypes for gene: ETFB were changed from to multiple acyl-CoA dehydrogenase deficiency MONDO:0009282
Mendeliome v0.14732 EXT1 Zornitza Stark Marked gene: EXT1 as ready
Mendeliome v0.14732 EXT1 Zornitza Stark Gene: ext1 has been classified as Green List (High Evidence).
Mendeliome v0.14732 EXT1 Zornitza Stark Phenotypes for gene: EXT1 were changed from to hereditary multiple osteochondromas MONDO:0005508; exostoses, multiple, type 1 MONDO:0007585
Mendeliome v0.14731 EYA4 Zornitza Stark Gene: eya4 has been classified as Green List (High Evidence).
Mendeliome v0.14731 EYS Zornitza Stark Gene: eys has been classified as Green List (High Evidence).
Mendeliome v0.14731 EYS Zornitza Stark Phenotypes for gene: EYS were changed from to Retinitis pigmentosa 25 MONDO:0011272
Mendeliome v0.14730 EYS Zornitza Stark Publications for gene: EYS were set to
Mendeliome v0.14729 EYS Zornitza Stark Mode of inheritance for gene: EYS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14728 FXR1 Zornitza Stark Gene: fxr1 has been classified as Green List (High Evidence).
Mendeliome v0.14728 ETV2 Ain Roesley Marked gene: ETV2 as ready
Mendeliome v0.14728 ETV2 Ain Roesley Gene: etv2 has been classified as Red List (Low Evidence).
Mendeliome v0.14728 ETV2 Ain Roesley gene: ETV2 was added
gene: ETV2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ETV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETV2 were set to 33359164
Phenotypes for gene: ETV2 were set to multiple fetal anomalies; congenital heart disease MONDO:000545, ETV2-related; vertebral malformations
Review for gene: ETV2 was set to RED
gene: ETV2 was marked as current diagnostic
Added comment: 1 family with 4 fetus-es, cHet for a fs (NMD-predicted) and a missense

3/4 vertebral malformations
2/4 Tetralogy of Fallot
1/4 arterial septal defect
1/4 ventricular septal defect, aortic dilatation
1/4 pre-axial polydactyly
Sources: Literature
Mendeliome v0.14727 GABRB2 Zornitza Stark Gene: gabrb2 has been classified as Green List (High Evidence).
Mendeliome v0.14727 GABRB2 Zornitza Stark Publications for gene: GABRB2 were set to
Mendeliome v0.14726 GALNT2 Zornitza Stark Marked gene: GALNT2 as ready
Mendeliome v0.14726 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence).
Mendeliome v0.14726 GALNT2 Zornitza Stark Phenotypes for gene: GALNT2 were changed from Congenital disorder of glycosylation to Congenital disorder of glycosylation MONDO:0015286
Mendeliome v0.14725 GALNT3 Zornitza Stark Marked gene: GALNT3 as ready
Mendeliome v0.14725 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
Mendeliome v0.14725 GALNT3 Zornitza Stark Phenotypes for gene: GALNT3 were changed from to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Mendeliome v0.14724 GALNT3 Zornitza Stark Publications for gene: GALNT3 were set to
Mendeliome v0.14723 GALNT3 Zornitza Stark Mode of inheritance for gene: GALNT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14722 GALT Zornitza Stark Marked gene: GALT as ready
Mendeliome v0.14722 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Mendeliome v0.14722 GALT Zornitza Stark Phenotypes for gene: GALT were changed from to Galactosaemia MIM#230400; Disorders of galactose metabolism
Mendeliome v0.14721 GALT Zornitza Stark Publications for gene: GALT were set to
Mendeliome v0.14720 GALT Zornitza Stark Mode of inheritance for gene: GALT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14719 GAMT Zornitza Stark Marked gene: GAMT as ready
Mendeliome v0.14719 GAMT Zornitza Stark Gene: gamt has been classified as Green List (High Evidence).
Mendeliome v0.14719 GAMT Zornitza Stark Phenotypes for gene: GAMT were changed from to Cerebral creatine deficiency syndrome 2 MIM#612736; Disorders of creatinine metabolism
Mendeliome v0.14718 GAMT Zornitza Stark Publications for gene: GAMT were set to
Mendeliome v0.14717 GAMT Zornitza Stark Mode of inheritance for gene: GAMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14716 GAN Zornitza Stark Gene: gan has been classified as Green List (High Evidence).
Mendeliome v0.14716 GAN Zornitza Stark Phenotypes for gene: GAN were changed from to Giant axonal neuropathy-1, MIM# 256850
Mendeliome v0.14715 GAN Zornitza Stark Publications for gene: GAN were set to
Mendeliome v0.14714 GAN Zornitza Stark Mode of inheritance for gene: GAN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14713 GBA2 Zornitza Stark Gene: gba2 has been classified as Green List (High Evidence).
Mendeliome v0.14713 GBA2 Zornitza Stark Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, MIM# 614409; MONDO:0013737
Mendeliome v0.14712 GBA2 Zornitza Stark Publications for gene: GBA2 were set to
Mendeliome v0.14711 GBA2 Zornitza Stark Mode of inheritance for gene: GBA2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14710 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Mendeliome v0.14710 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from to Glutaric aciduria, type I MIM#231670; Organic acidurias
Mendeliome v0.14709 GCDH Zornitza Stark Publications for gene: GCDH were set to
Mendeliome v0.14708 GCDH Zornitza Stark Mode of inheritance for gene: GCDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14707 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Mendeliome v0.14707 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
Mendeliome v0.14706 GCH1 Zornitza Stark Publications for gene: GCH1 were set to
Mendeliome v0.14705 GCH1 Zornitza Stark Mode of inheritance for gene: GCH1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14704 GCK Zornitza Stark Gene: gck has been classified as Green List (High Evidence).
Mendeliome v0.14704 GCK Zornitza Stark Phenotypes for gene: GCK were changed from to Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853); Diabetes mellitus, permanent neonatal 1, AR (MIM#606176); Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485); MODY, type II, AD (MIM#125851)
Mendeliome v0.14703 GCK Zornitza Stark Publications for gene: GCK were set to
Mendeliome v0.14702 GCK Zornitza Stark Mode of inheritance for gene: GCK was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14701 GCNT2 Zornitza Stark Marked gene: GCNT2 as ready
Mendeliome v0.14701 GCNT2 Zornitza Stark Gene: gcnt2 has been classified as Green List (High Evidence).
Mendeliome v0.14701 GDNF Elena Savva Phenotypes for gene: GDNF were changed from to {Hirschsprung disease, susceptibility to, 3} MIM#613711
Mendeliome v0.14700 GCNT2 Zornitza Stark Phenotypes for gene: GCNT2 were changed from to Cataract 13 with adult i phenotype, OMIM # 116700
Mendeliome v0.14700 GDNF Elena Savva Publications for gene: GDNF were set to
Mendeliome v0.14700 GDNF Elena Savva Mode of inheritance for gene: GDNF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14699 GCNT2 Zornitza Stark Publications for gene: GCNT2 were set to
Mendeliome v0.14698 GCNT2 Zornitza Stark Mode of inheritance for gene: GCNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14697 GDAP1 Zornitza Stark Gene: gdap1 has been classified as Green List (High Evidence).
Mendeliome v0.14697 GDAP1 Zornitza Stark Phenotypes for gene: GDAP1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2K 607831, MIM# Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM# 607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM# 608340; Charcot-Marie-Tooth disease, type 4A, MIM# 214400
Mendeliome v0.14696 ATPAF2 Elena Savva Mode of inheritance for gene: ATPAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14695 GATAD1 Elena Savva Phenotypes for gene: GATAD1 were changed from to ?Cardiomyopathy, dilated, 2B MIM#614672
Mendeliome v0.14694 GATAD1 Elena Savva Marked gene: GATAD1 as ready
Mendeliome v0.14694 GATAD1 Elena Savva Gene: gatad1 has been classified as Red List (Low Evidence).
Mendeliome v0.14694 GATAD1 Elena Savva Publications for gene: GATAD1 were set to
Mendeliome v0.14694 GATAD1 Elena Savva Mode of inheritance for gene: GATAD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14693 FBXW4 Elena Savva Gene: fbxw4 has been classified as Red List (Low Evidence).
Mendeliome v0.14693 AURKC Elena Savva Phenotypes for gene: AURKC were changed from to Spermatogenic failure 5 MIM #243060
Mendeliome v0.14692 AURKC Elena Savva Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14692 AURKC Elena Savva Mode of inheritance for gene: AURKC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14691 ATPAF2 Elena Savva Marked gene: ATPAF2 as ready
Mendeliome v0.14691 ATPAF2 Elena Savva Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14691 ATP2C2 Elena Savva Marked gene: ATP2C2 as ready
Mendeliome v0.14691 ATP2C2 Elena Savva Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.14691 AHSG Elena Savva Gene: ahsg has been classified as Red List (Low Evidence).
Mendeliome v0.14691 GDAP1 Zornitza Stark Publications for gene: GDAP1 were set to
Mendeliome v0.14690 GDAP1 Zornitza Stark Mode of inheritance for gene: GDAP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14689 GDF2 Zornitza Stark Gene: gdf2 has been classified as Green List (High Evidence).
Mendeliome v0.14689 GDF2 Zornitza Stark Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506; pulmonary arteriovenous malformations
Mendeliome v0.14688 GDF2 Zornitza Stark Publications for gene: GDF2 were set to
Mendeliome v0.14687 GDF2 Zornitza Stark Mode of inheritance for gene: GDF2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14686 GDF9 Zornitza Stark Gene: gdf9 has been classified as Green List (High Evidence).
Mendeliome v0.14686 GDF9 Zornitza Stark Phenotypes for gene: GDF9 were changed from to Premature ovarian failure 14, OMIM# 618014
Mendeliome v0.14685 GDF9 Zornitza Stark Publications for gene: GDF9 were set to
Mendeliome v0.14684 GDF9 Zornitza Stark Mode of inheritance for gene: GDF9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14683 GEMIN4 Zornitza Stark Gene: gemin4 has been classified as Green List (High Evidence).
Mendeliome v0.14683 GEMIN4 Zornitza Stark Phenotypes for gene: GEMIN4 were changed from to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913
Mendeliome v0.14682 GEMIN4 Zornitza Stark Publications for gene: GEMIN4 were set to
Mendeliome v0.14681 GEMIN4 Zornitza Stark Mode of inheritance for gene: GEMIN4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14680 GFM2 Zornitza Stark Gene: gfm2 has been classified as Green List (High Evidence).
Mendeliome v0.14680 GFM2 Zornitza Stark Phenotypes for gene: GFM2 were changed from to Combined oxidative phosphorylation deficiency 39, OMIM #618397
Mendeliome v0.14679 GFM2 Zornitza Stark Publications for gene: GFM2 were set to
Mendeliome v0.14678 GFM2 Zornitza Stark Mode of inheritance for gene: GFM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14677 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Mendeliome v0.14677 GIF Zornitza Stark Phenotypes for gene: GIF were changed from to Intrinsic factor deficiency MIM#261000; Disorders of cobalamin absorption, transport and metabolism
Mendeliome v0.14676 GIF Zornitza Stark Publications for gene: GIF were set to
Mendeliome v0.14675 GIF Zornitza Stark Mode of inheritance for gene: GIF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14674 KATNB1 Elena Savva reviewed gene: KATNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25521378, 25521379, 26640080; Phenotypes: Lissencephaly 6, with microcephaly MIM#616212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14674 PRKAG3 Elena Savva Phenotypes for gene: PRKAG3 were changed from increased glycogen content in skeletal muscle; [Skeletal muscle glycogen content and metabolism QTL] MIM#619030 to increased glycogen content in skeletal muscle
Mendeliome v0.14673 TIA1 Elena Savva Publications for gene: TIA1 were set to
Mendeliome v0.14672 SLC26A1 Elena Savva Gene: slc26a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14672 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454) to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14671 PRKAG3 Elena Savva Phenotypes for gene: PRKAG3 were changed from to increased glycogen content in skeletal muscle; [Skeletal muscle glycogen content and metabolism QTL] MIM#619030
Mendeliome v0.14670 PRKAG3 Elena Savva Gene: prkag3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14670 GINS1 Zornitza Stark Gene: gins1 has been classified as Green List (High Evidence).
Mendeliome v0.14670 GINS1 Zornitza Stark Publications for gene: GINS1 were set to
Mendeliome v0.14669 PRKAG3 Elena Savva Publications for gene: PRKAG3 were set to
Mendeliome v0.14668 PRKAG3 Elena Savva Mode of inheritance for gene: PRKAG3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14667 U2AF2 Elena Savva Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14667 TDP1 Elena Savva Marked gene: TDP1 as ready
Mendeliome v0.14667 TDP1 Elena Savva Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14667 TIA1 Elena Savva Phenotypes for gene: TIA1 were changed from to Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133; Welander distal myopathy (MIM#604454)
Mendeliome v0.14666 TIA1 Elena Savva Marked gene: TIA1 as ready
Mendeliome v0.14666 TIA1 Elena Savva Gene: tia1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 PLD3 Elena Savva Gene: pld3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 RBM7 Elena Savva Gene: rbm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 MFAP5 Elena Savva Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 MMGT1 Elena Savva Marked gene: MMGT1 as ready
Mendeliome v0.14666 MMGT1 Elena Savva Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 FRA12A Elena Savva Marked STR: FRA12A as ready
Mendeliome v0.14666 FRA12A Elena Savva Str: fra12a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 GIGYF2 Elena Savva Gene: gigyf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14666 FRA12A Elena Savva Phenotypes for STR: FRA12A were changed from Mental retardation, FRA12A type MIM#136630 to Intellectual developmental disorder, autosomal dominant, FRA12A type MIM#136630
Mendeliome v0.14665 MEPE Elena Savva Gene: mepe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14665 LRIF1 Elena Savva Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14665 GIGYF2 Elena Savva Phenotypes for gene: GIGYF2 were changed from to {Parkinson disease 11} MIM#607688
Mendeliome v0.14664 GIGYF2 Elena Savva Mode of inheritance for gene: GIGYF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14663 DMGDH Elena Savva Gene: dmgdh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14663 DMGDH Elena Savva Phenotypes for gene: DMGDH were changed from to Dimethylglycine dehydrogenase deficiency MIM#605850; Disorders and variants of other enzymes that oxidise xenobiotics
Mendeliome v0.14663 DMGDH Elena Savva Publications for gene: DMGDH were set to
Mendeliome v0.14662 DCAF8 Elena Savva Gene: dcaf8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 CCT5 Elena Savva Marked gene: CCT5 as ready
Mendeliome v0.14662 CCT5 Elena Savva Gene: cct5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 ATG5 Elena Savva Marked gene: ATG5 as ready
Mendeliome v0.14662 ATG5 Elena Savva Gene: atg5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14662 LYZ Abhijit Kulkarni reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 1808634 8464497 15745733; Phenotypes: Amyloidosis, renal (MIM: 105200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14662 USP8 Elena Savva Gene: usp8 has been classified as Green List (High Evidence).
Mendeliome v0.14662 LRP5 Krithika Murali reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Exudative vitreoretinopathy 4 - MIM#601813 (AD, AR), Hyperostosis, endosteal - MIM#144750 (AD), Osteopetrosis, autosomal dominant 1 - MIM#607634(AD), Osteoporosis-pseudoglioma syndrome - MIM#259770 (AR), Osteosclerosis - #144750 (AD), Polycystic liver disease 4 with or without kidney cysts - MIM#617875 (AD), van Buchem disease, type 2 - MIM#607636; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14662 MSX1 Elena Savva Phenotypes for gene: MSX1 were changed from Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia to Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia
Mendeliome v0.14661 MSX1 Elena Savva Publications for gene: MSX1 were set to 33419968, 33708320, 32192766
Mendeliome v0.14660 LRP6 Krithika Murali reviewed gene: LRP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26387593; Phenotypes: Tooth agenesis, selective, 7 - MIM#616724; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14660 LYRM7 Krithika Murali reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8 - MIM#615838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14660 LYST Krithika Murali reviewed gene: LYST: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chediak-Higashi syndrome - MIM#214500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14660 MSX1 Elena Savva Phenotypes for gene: MSX1 were changed from to Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia
Mendeliome v0.14659 MSX1 Elena Savva Publications for gene: MSX1 were set to
Mendeliome v0.14659 MSX1 Elena Savva Gene: msx1 has been classified as Green List (High Evidence).
Mendeliome v0.14659 MSX1 Elena Savva Mode of inheritance for gene: MSX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14658 LYZ Krithika Murali reviewed gene: LYZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 1808634, 8464497, 15745733,; Phenotypes: Amyloidosis, renal - MIM#105200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14658 GINS1 Zornitza Stark Mode of inheritance for gene: GINS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14657 GJA1 Zornitza Stark Gene: gja1 has been classified as Green List (High Evidence).
Mendeliome v0.14657 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from to Oculodentodigital dysplasia, autosomal recessive, MIM# 257850; Oculodentodigital dysplasia, MIM# 164200
Mendeliome v0.14656 GJA1 Zornitza Stark Publications for gene: GJA1 were set to
Mendeliome v0.14655 GJA1 Zornitza Stark Mode of inheritance for gene: GJA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14654 GJA5 Zornitza Stark Gene: gja5 has been classified as Green List (High Evidence).
Mendeliome v0.14654 GJA5 Zornitza Stark Phenotypes for gene: GJA5 were changed from to Atrial fibrillation, familial, 11, OMIM# 614049
Mendeliome v0.14653 GJA5 Zornitza Stark Publications for gene: GJA5 were set to
Mendeliome v0.14652 GJA5 Zornitza Stark Mode of inheritance for gene: GJA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14651 LRP2 Chirag Patel commented on gene: LRP2: Donnai-Barrow syndrome (DBS) was first described as a distinct disorder characterized by diaphragmatic hernia, exomphalos, absent corpus callosum, myopia, agenesis of the corpus callosum and proteinuria, and sensorineural deafness.

Kantarci et al. (2007) identified biallelic LRP2 mutations in 6 families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome.
Mendeliome v0.14651 LRP2 Chirag Patel reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17632512; Phenotypes: Donnai-Barrow syndrome, MIM#222448; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14651 LINS1 Chirag Patel reviewed gene: LINS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32802957, 34450347, 32499722, 31922598; Phenotypes: Intellectual developmental disorder, autosomal recessive 27, MIM# 614340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14651 ATPAF2 Krithika Murali reviewed gene: ATPAF2: Rating: RED; Mode of pathogenicity: None; Publications: 14757859; Phenotypes: ?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 - MIM#604273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14651 ADD1 Chirag Patel Classified gene: ADD1 as Green List (high evidence)
Mendeliome v0.14651 ADD1 Chirag Patel Gene: add1 has been classified as Green List (High Evidence).
Mendeliome v0.14650 ADD1 Chirag Patel gene: ADD1 was added
gene: ADD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ADD1 were set to PMID: 34906466
Phenotypes for gene: ADD1 were set to Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM #
Review for gene: ADD1 was set to GREEN
Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown
Sources: Literature
Mendeliome v0.14649 AVP Chirag Patel reviewed gene: AVP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 6526016, 1840604, 8554046; Phenotypes: Diabetes insipidus, neurohypophyseal MIM#125700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14649 AURKC Chirag Patel Classified gene: AURKC as Red List (low evidence)
Mendeliome v0.14649 AURKC Chirag Patel Gene: aurkc has been classified as Red List (Low Evidence).
Mendeliome v0.14648 AURKC Chirag Patel reviewed gene: AURKC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 5 , OMIM #243060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14648 ATPAF2 Chirag Patel Classified gene: ATPAF2 as Red List (low evidence)
Mendeliome v0.14648 ATPAF2 Chirag Patel Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14648 ATPAF2 Chirag Patel Classified gene: ATPAF2 as Red List (low evidence)
Mendeliome v0.14648 ATPAF2 Chirag Patel Gene: atpaf2 has been classified as Red List (Low Evidence).
Mendeliome v0.14647 ATPAF2 Chirag Patel reviewed gene: ATPAF2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 14757859; Phenotypes: ?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, OMIM# 604273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14647 ATP6V1E1 Chirag Patel reviewed gene: ATP6V1E1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28065471, 27023906; Phenotypes: Cutis laxa, autosomal recessive, type IIC MIM#617402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14647 ATP2A1 Chirag Patel reviewed gene: ATP2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32040565; Phenotypes: Brody myopathy, OMIM # 601003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14647 GJA5 Chirag Patel commented on gene: GJA5: Gollob et al. (2006) presented evidence that tissue-specific mutations in the GJA5 gene may predispose the atria to fibrillation. They identified a heterozygous missense mutation in blood and cardiac tissue in patient with AF. They also found 3 heterozygous missense mutations in cardiac tissue only in 3 other patients, indicating a somatic source of the genetic defects

Yang et al. (2010) identified a heterozygous nonsense mutationin a 64-year-old female patient who was diagnosed with paroxysmal AF at 32 years of age. The mutation was detected in 6 additional affected family members, but was not found in 6 unaffected family members or in 200 ethnically matched controls.

Yang et al. (2010) identified 3 heterozygous missense mutations in 3 probands with AF. The mutations segregated with disease in all 3 families and were not found in 200 ethnically matched controls.

Sun et al. (2013) identified a heterozygous missense mutation in a 42-year-old woman who had been diagnosed with AF at age 40 years. The mutation was also detected in her father, who had been diagnosed with lone AF at 41 years of age, but it was not found in unaffected family members, in 200 controls, or in the dbSNP database. Functional analysis demonstrated that the I75F mutant is unable to form functional gap junction channels and also impairs coupling when expressed with wildtype CX40 or CX43.
Mendeliome v0.14647 GJA5 Chirag Patel reviewed gene: GJA5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16790700, 20818502, 20650941, 23348765; Phenotypes: Atrial fibrillation, familial, 11, OMIM# 614049; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14647 GEMIN4 Chirag Patel reviewed gene: GEMIN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25558065, 30237576, 27878435; Phenotypes: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14647 GJB2 Zornitza Stark Gene: gjb2 has been classified as Green List (High Evidence).
Mendeliome v0.14647 GJB2 Zornitza Stark Phenotypes for gene: GJB2 were changed from to Bart-Pumphrey syndrome, MIM#149200; Deafness, autosomal dominant 3A, MIM#601544; Deafness, autosomal recessive 1A, MIM#220290; Hystrix-like ichthyosis with deafness, MIM#602540; Keratitis-ichthyosis-deafness syndrome, MIM#148210; Keratoderma, palmoplantar, with deafness, MIM#148350; Vohwinkel syndrome, MIM# 124500
Mendeliome v0.14646 GJB2 Zornitza Stark Publications for gene: GJB2 were set to
Mendeliome v0.14645 GJB2 Zornitza Stark Mode of inheritance for gene: GJB2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14644 GJB3 Zornitza Stark Gene: gjb3 has been classified as Green List (High Evidence).
Mendeliome v0.14644 GJB3 Zornitza Stark Phenotypes for gene: GJB3 were changed from to Erythrokeratodermia variabilis et progressiva 1, MIM# 133200
Mendeliome v0.14643 GJB3 Zornitza Stark Publications for gene: GJB3 were set to
Mendeliome v0.14642 GJB2 Chirag Patel reviewed gene: GJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11179004, 9529365, 14985372, 19941053, 11354642; Phenotypes: Bart-Pumphrey syndrome, MIM#149200, Deafness, autosomal dominant 3A, MIM#601544, Deafness, autosomal recessive 1A, MIM#220290, Hystrix-like ichthyosis with deafness, MIM#602540, Keratitis-ichthyosis-deafness syndrome, MIM#148210, Keratoderma, palmoplantar, with deafness, MIM#148350, Vohwinkel syndrome, MIM# 124500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14642 GJB3 Zornitza Stark Mode of inheritance for gene: GJB3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14641 GJB3 Zornitza Stark Mode of inheritance for gene: GJB3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14640 GJB3 Zornitza Stark reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843209, 10594760, 10798362, 12019212; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, MIM# 133200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14640 GJB3 Chirag Patel reviewed gene: GJB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9843209, 10798362, 10594760, 17446259, 9843210; Phenotypes: Erythrokeratodermia variabilis et progressiva 1, OMIM #133200, Deafness, autosomal dominant 2B, OMIM # 612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14640 GNB5 Chirag Patel reviewed gene: GNB5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27523599, 27677260, 28697420, 29368331; Phenotypes: Intellectual developmental disorder with cardiac arrhythmia, OMIM #617173, Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, OMIM # 617182, Early infantile epileptic encephalopathy (EIEE); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14640 GJB4 Zornitza Stark Gene: gjb4 has been classified as Green List (High Evidence).
Mendeliome v0.14640 GJB4 Zornitza Stark Phenotypes for gene: GJB4 were changed from to Erythrokeratodermia variabilis et progressiva 2, MIM# 617524
Mendeliome v0.14639 GJB4 Zornitza Stark Publications for gene: GJB4 were set to
Mendeliome v0.14638 GJB4 Zornitza Stark Mode of inheritance for gene: GJB4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14637 GJB4 Zornitza Stark reviewed gene: GJB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017804, 12648223, 19291775; Phenotypes: Erythrokeratodermia variabilis et progressiva 2, MIM# 617524; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14637 GJB6 Zornitza Stark Gene: gjb6 has been classified as Green List (High Evidence).
Mendeliome v0.14637 GJB6 Zornitza Stark Phenotypes for gene: GJB6 were changed from to Deafness, autosomal dominant 3B, MIM# 612643; Deafness, autosomal recessive 1B, MIM# 612645; Ectodermal dysplasia 2, Clouston type, MIM# 129500
Mendeliome v0.14636 GJB6 Zornitza Stark Publications for gene: GJB6 were set to
Mendeliome v0.14635 GJB6 Zornitza Stark Mode of inheritance for gene: GJB6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14634 GJB6 Zornitza Stark Tag SV/CNV tag was added to gene: GJB6.
Mendeliome v0.14634 GJB6 Zornitza Stark reviewed gene: GJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017065, 23219093, 11874494, 18717672, 27137747, 25808784, 19416251, 26620415, 17227867; Phenotypes: Deafness, autosomal dominant 3B, MIM# 612643, Deafness, autosomal recessive 1B, MIM# 612645, Ectodermal dysplasia 2, Clouston type, MIM# 129500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14634 GK Zornitza Stark Gene: gk has been classified as Green List (High Evidence).
Mendeliome v0.14634 GK Zornitza Stark Phenotypes for gene: GK were changed from to Glycerol kinase deficiency MIM#307030; Disorders of glycerol metabolism
Mendeliome v0.14633 GK Zornitza Stark Publications for gene: GK were set to
Mendeliome v0.14632 GK Zornitza Stark Mode of inheritance for gene: GK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14631 GLCCI1 Zornitza Stark Gene: glcci1 has been classified as Red List (Low Evidence).
Mendeliome v0.14631 GLCCI1 Zornitza Stark Phenotypes for gene: GLCCI1 were changed from to {Glucocorticoid therapy, response to} 614400
Mendeliome v0.14630 GLCCI1 Zornitza Stark Mode of inheritance for gene: GLCCI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14629 GLCCI1 Zornitza Stark Classified gene: GLCCI1 as Red List (low evidence)
Mendeliome v0.14629 GLCCI1 Zornitza Stark Gene: glcci1 has been classified as Red List (Low Evidence).
Mendeliome v0.14628 GLCCI1 Zornitza Stark reviewed gene: GLCCI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Glucocorticoid therapy, response to} 614400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14628 GLE1 Zornitza Stark Gene: gle1 has been classified as Green List (High Evidence).
Mendeliome v0.14628 GLE1 Zornitza Stark Phenotypes for gene: GLE1 were changed from to Lethal congenital contracture syndrome 1, MIM# 253310
Mendeliome v0.14627 GLE1 Zornitza Stark Publications for gene: GLE1 were set to
Mendeliome v0.14626 GLE1 Zornitza Stark Mode of inheritance for gene: GLE1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14625 GLE1 Zornitza Stark Tag founder tag was added to gene: GLE1.
Mendeliome v0.14625 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Mendeliome v0.14625 GLIS3 Zornitza Stark Phenotypes for gene: GLIS3 were changed from to Diabetes mellitus, neonatal, with congenital hypothyroidism, MIM#610199
Mendeliome v0.14624 GLIS3 Zornitza Stark Publications for gene: GLIS3 were set to
Mendeliome v0.14623 GLIS3 Zornitza Stark Mode of inheritance for gene: GLIS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14622 GLIS3 Zornitza Stark reviewed gene: GLIS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21139041, 35410112, 35394098, 34093443; Phenotypes: Diabetes mellitus, neonatal, with congenital hypothyroidism, MIM#610199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14622 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Mendeliome v0.14622 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Glutamine deficiency, congenital MIM#610015; disorder of amino acid metabolism
Mendeliome v0.14621 GLUL Zornitza Stark Publications for gene: GLUL were set to
Mendeliome v0.14620 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14619 GLYCTK Zornitza Stark Marked gene: GLYCTK as ready
Mendeliome v0.14619 GLYCTK Zornitza Stark Gene: glyctk has been classified as Green List (High Evidence).
Mendeliome v0.14619 GLYCTK Zornitza Stark Phenotypes for gene: GLYCTK were changed from to D-glyceric aciduria MIM#220120; Disorders of serine, glycine or glycerate metabolism
Mendeliome v0.14618 GLYCTK Zornitza Stark Publications for gene: GLYCTK were set to
Mendeliome v0.14617 GLYCTK Zornitza Stark Mode of inheritance for gene: GLYCTK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14616 GMPPA Zornitza Stark Gene: gmppa has been classified as Green List (High Evidence).
Mendeliome v0.14616 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from to Alacrima, achalasia, and mental retardation syndrome, MIM# 615510
Mendeliome v0.14615 GMPPA Zornitza Stark Publications for gene: GMPPA were set to
Mendeliome v0.14614 GMPPA Zornitza Stark Mode of inheritance for gene: GMPPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14613 GMPPA Zornitza Stark reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24035193, 28574218; Phenotypes: Alacrima, achalasia, and mental retardation syndrome, MIM# 615510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14613 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Mendeliome v0.14613 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352
Mendeliome v0.14612 GMPPB Zornitza Stark Mode of inheritance for gene: GMPPB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14611 GMPPB Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14611 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Mendeliome v0.14611 GNAS Zornitza Stark Phenotypes for gene: GNAS were changed from to Osseous heteroplasia, progressive (166350) AD; Pituitary adenoma 3, multiple types, somatic (617686); Pseudohypoparathyroidism Ia (103580) AD; Pseudohypoparathyroidism Ib (603233) AD; Pseudohypoparathyroidism Ic (612462) AD; Pseudopseudohypoparathyroidism (612463)
Mendeliome v0.14610 GNAS Zornitza Stark Mode of inheritance for gene: GNAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14609 GNAS Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osseous heteroplasia, progressive (166350) AD, Pituitary adenoma 3, multiple types, somatic (617686), Pseudohypoparathyroidism Ia (103580) AD, Pseudohypoparathyroidism Ib (603233) AD, Pseudohypoparathyroidism Ic (612462) AD, Pseudopseudohypoparathyroidism (612463); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14609 GNAT1 Zornitza Stark Marked gene: GNAT1 as ready
Mendeliome v0.14609 GNAT1 Zornitza Stark Gene: gnat1 has been classified as Green List (High Evidence).
Mendeliome v0.14609 GNAT1 Zornitza Stark Phenotypes for gene: GNAT1 were changed from to Night blindness, congenital stationary, autosomal dominant 3, MIM# 610444; Night blindness, congenital stationary, type 1G, MIM# 616389
Mendeliome v0.14608 GNAT1 Zornitza Stark Publications for gene: GNAT1 were set to
Mendeliome v0.14607 GNAT1 Zornitza Stark Mode of inheritance for gene: GNAT1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14606 GNAT1 Zornitza Stark reviewed gene: GNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8673138, 17584859, 22190596, 26472407, 11095744, 11095744, 30051303; Phenotypes: Night blindness, congenital stationary, autosomal dominant 3, MIM# 610444, Night blindness, congenital stationary, type 1G, MIM# 616389; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14606 GNB3 Zornitza Stark Gene: gnb3 has been classified as Green List (High Evidence).
Mendeliome v0.14606 GNB3 Zornitza Stark Phenotypes for gene: GNB3 were changed from to Night blindness, congenital stationary, type 1H, MIM# 617024
Mendeliome v0.14605 GNB3 Zornitza Stark Publications for gene: GNB3 were set to
Mendeliome v0.14604 GNB3 Zornitza Stark Mode of inheritance for gene: GNB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14603 GNB3 Zornitza Stark reviewed gene: GNB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27063057, 17065478; Phenotypes: Night blindness, congenital stationary, type 1H, MIM# 617024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14603 GNMT Zornitza Stark Marked gene: GNMT as ready
Mendeliome v0.14603 GNMT Zornitza Stark Gene: gnmt has been classified as Green List (High Evidence).
Mendeliome v0.14603 GNMT Zornitza Stark Phenotypes for gene: GNMT were changed from to Glycine N-methyltransferase deficiency MIM#606664; Disorders of the metabolism of sulphur amino acids
Mendeliome v0.14602 GNMT Zornitza Stark Publications for gene: GNMT were set to
Mendeliome v0.14601 GNMT Zornitza Stark Mode of inheritance for gene: GNMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14600 GOSR2 Zornitza Stark Gene: gosr2 has been classified as Green List (High Evidence).
Mendeliome v0.14600 GOSR2 Zornitza Stark Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6 , MIM#614018
Mendeliome v0.14599 GOSR2 Zornitza Stark Publications for gene: GOSR2 were set to
Mendeliome v0.14598 GOSR2 Zornitza Stark Mode of inheritance for gene: GOSR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14597 GOSR2 Zornitza Stark reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21549339, 24458321, 30363482; Phenotypes: Epilepsy, progressive myoclonic 6 , MIM#614018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14597 GOT1 Zornitza Stark Marked gene: GOT1 as ready
Mendeliome v0.14597 GOT1 Zornitza Stark Gene: got1 has been classified as Red List (Low Evidence).
Mendeliome v0.14597 GOT1 Zornitza Stark Phenotypes for gene: GOT1 were changed from to Aspartate aminotransferase, serum level of, QTL1, MIM# 614419
Mendeliome v0.14596 GOT1 Zornitza Stark Classified gene: GOT1 as Red List (low evidence)
Mendeliome v0.14596 GOT1 Zornitza Stark Gene: got1 has been classified as Red List (Low Evidence).
Mendeliome v0.14595 GOT1 Zornitza Stark reviewed gene: GOT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aspartate aminotransferase, serum level of, QTL1, MIM# 614419; Mode of inheritance: None
Mendeliome v0.14595 GPC4 Zornitza Stark Gene: gpc4 has been classified as Green List (High Evidence).
Mendeliome v0.14595 GPC4 Zornitza Stark Phenotypes for gene: GPC4 were changed from to Keipert syndrome OMIM# 301026
Mendeliome v0.14594 GPC4 Zornitza Stark Publications for gene: GPC4 were set to
Mendeliome v0.14593 GPC4 Zornitza Stark Mode of inheritance for gene: GPC4 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14592 GPNMB Krithika Murali Deleted their review
Mendeliome v0.14592 GPNMB Krithika Murali reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31226264, 29336782, 31260093, 34551863, 33687658; Phenotypes: Amyloidosis, primary localized cutaneous, 3 - MIM#617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14592 GLE1 Chirag Patel reviewed gene: GLE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18204449, 22357925; Phenotypes: Lethal congenital contracture syndrome 1, MIM# 253310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14592 GDF2 Chirag Patel reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23972370, 27081547, 32573726, 32992168, 34611981, 33834622, 32669404, 26056270, 23972370; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5 OMIM # 615506, pulmonary arteriovenous malformations; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14592 GCNT2 Chirag Patel reviewed gene: GCNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15161861, 27936067, 12424189, 28224043; Phenotypes: Cataract 13 with adult i phenotype, OMIM # 116700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14592 GJA1 Chirag Patel reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19338053; Phenotypes: Oculodentodigital dysplasia, autosomal recessive, MIM# 257850, Oculodentodigital dysplasia, MIM# 164200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14592 GCK Chirag Patel reviewed gene: GCK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19790256; Phenotypes: Diabetes mellitus, noninsulin-dependent, late onset, AD (MIM#125853), Diabetes mellitus, permanent neonatal 1, AR (MIM#606176), Hyperinsulinemic hypoglycemia, familial, 3, AD (MIM#602485), MODY, type II, AD (MIM#125851); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14592 GINS1 Chirag Patel reviewed gene: GINS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28414293; Phenotypes: Immunodeficiency 55, OMIM #617827; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14592 GDNF Chirag Patel Classified gene: GDNF as Red List (low evidence)
Mendeliome v0.14592 GDNF Chirag Patel Gene: gdnf has been classified as Red List (Low Evidence).
Mendeliome v0.14591 GDNF Chirag Patel reviewed gene: GDNF: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 8896568, 8968758; Phenotypes: {Hirschsprung disease, susceptibility to, 3}, OMIM # 613711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14591 GFM2 Chirag Patel reviewed gene: GFM2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22700954, 26016410, 29075935; Phenotypes: Combined oxidative phosphorylation deficiency 39, OMIM #618397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14591 GDF9 Chirag Patel reviewed gene: GDF9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29044499, 8849725, 33036707; Phenotypes: Premature ovarian failure 14, OMIM# 618014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14591 GIGYF2 Chirag Patel Publications for gene: GIGYF2 were set to
Mendeliome v0.14590 GIGYF2 Chirag Patel Classified gene: GIGYF2 as Amber List (moderate evidence)
Mendeliome v0.14590 GIGYF2 Chirag Patel Gene: gigyf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14589 GIGYF2 Chirag Patel reviewed gene: GIGYF2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18358451; Phenotypes: {Parkinson disease 11} , OMIM # 607688; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14589 HEY2 Zornitza Stark Gene: hey2 has been classified as Red List (Low Evidence).
Mendeliome v0.14589 HEY2 Zornitza Stark Phenotypes for gene: HEY2 were changed from congenital heart defects and thoracic aortic aneurysms to congenital heart disease MONDO:0005453; thoracic aortic aneurysms
Mendeliome v0.14588 GCH1 Chirag Patel reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 7874165, 11113234, 15753436, 9667588, 10987649, 32170445, 32278297, 32746945, 30314816; Phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14588 IL18BP Zornitza Stark Gene: il18bp has been classified as Red List (Low Evidence).
Mendeliome v0.14588 ITPKB Zornitza Stark Marked gene: ITPKB as ready
Mendeliome v0.14588 ITPKB Zornitza Stark Gene: itpkb has been classified as Red List (Low Evidence).
Mendeliome v0.14588 ITPKB Zornitza Stark Phenotypes for gene: ITPKB were changed from Severe combined immunodeficiency, absent T cells, present B cells and NK cells to Severe combined immunodeficiency MONDO:0015974, absent T cells, present B cells and NK cells
Mendeliome v0.14587 MUC7 Zornitza Stark Gene: muc7 has been classified as Red List (Low Evidence).
Mendeliome v0.14587 MUC7 Zornitza Stark Phenotypes for gene: MUC7 were changed from to {Asthma, protection against} MIM#600807
Mendeliome v0.14586 MUC7 Zornitza Stark Mode of inheritance for gene: MUC7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14585 MYF6 Zornitza Stark Gene: myf6 has been classified as Red List (Low Evidence).
Mendeliome v0.14585 MYF6 Zornitza Stark Phenotypes for gene: MYF6 were changed from to Centronuclear myopathy, MONDO:0018947
Mendeliome v0.14584 MYF6 Zornitza Stark Publications for gene: MYF6 were set to
Mendeliome v0.14583 MYF6 Zornitza Stark Mode of inheritance for gene: MYF6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14582 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14582 PDCD6IP Zornitza Stark Phenotypes for gene: PDCD6IP were changed from Microcephaly; intellectual disability to Neurodevelopmental disorder MONDO:0700092; Microcephaly; intellectual disability
Mendeliome v0.14581 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Mendeliome v0.14581 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14580 POU5F1 Zornitza Stark Gene: pou5f1 has been classified as Red List (Low Evidence).
Mendeliome v0.14580 GBA2 Chirag Patel reviewed gene: GBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23332916, 23332917, 29524657; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM# 614409, MONDO:0013737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14580 GATAD1 Chirag Patel Classified gene: GATAD1 as Red List (low evidence)
Mendeliome v0.14580 GATAD1 Chirag Patel Gene: gatad1 has been classified as Red List (Low Evidence).
Mendeliome v0.14579 SGK3 Zornitza Stark Gene: sgk3 has been classified as Red List (Low Evidence).
Mendeliome v0.14579 GATAD1 Chirag Patel reviewed gene: GATAD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21965549; Phenotypes: ?Cardiomyopathy, dilated, 2B, OMIM # 614672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14579 DMPK Zornitza Stark Gene: dmpk has been removed from the panel.
Mendeliome v0.14579 NOP56 Zornitza Stark Gene: nop56 has been removed from the panel.
Mendeliome v0.14579 NOP56 Zornitza Stark Tag STR tag was added to gene: NOP56.
Mendeliome v0.14579 GAN Chirag Patel reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11062483; Phenotypes: Giant axonal neuropathy-1, MIM# 256850; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14579 GALNT3 Chirag Patel reviewed gene: GALNT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15133511, 20358599, 32125652; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14579 GPD1 Zornitza Stark Gene: gpd1 has been classified as Green List (High Evidence).
Mendeliome v0.14579 GPD1 Zornitza Stark Phenotypes for gene: GPD1 were changed from to Hypertriglyceridemia, transient infantile MIM#614480; glycerol-3-phosphate dehydrogenase deficiency
Mendeliome v0.14578 GPD1 Zornitza Stark Publications for gene: GPD1 were set to
Mendeliome v0.14577 GPD1 Zornitza Stark Mode of inheritance for gene: GPD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14576 GPD1 Zornitza Stark reviewed gene: GPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22226083, 24549054, 35365473, 34484308, 33447932; Phenotypes: Hypertriglyceridaemia, transient infantile, MIM# 614480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14576 GPHN Zornitza Stark Gene: gphn has been classified as Green List (High Evidence).
Mendeliome v0.14576 GPHN Zornitza Stark Publications for gene: GPHN were set to 22040219; 11095995; 26613940; 24561070; 23393157
Mendeliome v0.14575 GPNMB Zornitza Stark Gene: gpnmb has been classified as Green List (High Evidence).
Mendeliome v0.14575 GPNMB Zornitza Stark Phenotypes for gene: GPNMB were changed from to Amyloidosis, primary localized cutaneous, 3, MIM# 617920
Mendeliome v0.14574 GPNMB Zornitza Stark Publications for gene: GPNMB were set to
Mendeliome v0.14573 GPNMB Zornitza Stark Mode of inheritance for gene: GPNMB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14572 GPNMB Zornitza Stark reviewed gene: GPNMB: Rating: GREEN; Mode of pathogenicity: None; Publications: 29336782; Phenotypes: Amyloidosis, primary localized cutaneous, 3, MIM# 617920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14572 GREM1 Zornitza Stark Gene: grem1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14572 GREM1 Zornitza Stark Phenotypes for gene: GREM1 were changed from to Genetic intestinal polyposis MONDO:0018188
Mendeliome v0.14571 GREM1 Zornitza Stark Publications for gene: GREM1 were set to
Mendeliome v0.14570 GREM1 Zornitza Stark Mode of inheritance for gene: GREM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14569 GREM1 Zornitza Stark Tag SV/CNV tag was added to gene: GREM1.
Mendeliome v0.14569 GREM1 Zornitza Stark Classified gene: GREM1 as Amber List (moderate evidence)
Mendeliome v0.14569 GREM1 Zornitza Stark Gene: grem1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14568 MRAP Zornitza Stark Gene: mrap has been classified as Green List (High Evidence).
Mendeliome v0.14568 MRAP Zornitza Stark Phenotypes for gene: MRAP were changed from to Glucocorticoid deficiency 2, MIM# 607398
Mendeliome v0.14567 MRAP Zornitza Stark Publications for gene: MRAP were set to
Mendeliome v0.14566 MRAP Zornitza Stark Mode of inheritance for gene: MRAP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14565 MRAP Zornitza Stark reviewed gene: MRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15654338; Phenotypes: Glucocorticoid deficiency 2, MIM# 607398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14565 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Green List (High Evidence).
Mendeliome v0.14565 MPZL2 Zornitza Stark Phenotypes for gene: MPZL2 were changed from to Deafness, autosomal recessive 111, MIM#618145
Mendeliome v0.14564 MPZL2 Zornitza Stark Publications for gene: MPZL2 were set to
Mendeliome v0.14563 MPZL2 Zornitza Stark Mode of inheritance for gene: MPZL2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14562 MPZL2 Zornitza Stark reviewed gene: MPZL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29982980, 29961571; Phenotypes: Deafness, autosomal recessive 111, MIM#618145; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14562 MPZ Zornitza Stark Gene: mpz has been classified as Green List (High Evidence).
Mendeliome v0.14562 MPZ Zornitza Stark Phenotypes for gene: MPZ were changed from to Charcot Marie Tooth disease, dominant intermediate D, 60779; Neuropathy, congenital hypomyelinating, 605253; Charcot Marie Tooth disease, type 2J, 607736; Dejerine Sottas disease, 145900; Charcot Marie Tooth disease, type 1B, 118200; Charcot Marie Tooth disease, type 2I, 607677; HMSN
Mendeliome v0.14561 MPZ Zornitza Stark Publications for gene: MPZ were set to
Mendeliome v0.14560 MPZ Zornitza Stark Mode of inheritance for gene: MPZ was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14559 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Mendeliome v0.14559 MPV17 Zornitza Stark Phenotypes for gene: MPV17 were changed from to Charcot-Marie-Tooth disease, axonal, type 2EE, MIM# 618400
Mendeliome v0.14558 MPV17 Zornitza Stark Publications for gene: MPV17 were set to
Mendeliome v0.14557 MPV17 Zornitza Stark Mode of inheritance for gene: MPV17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14556 MPO Zornitza Stark Gene: mpo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14556 MPO Zornitza Stark Phenotypes for gene: MPO were changed from to Myeloperoxidase deficiency, MIM# 254600
Mendeliome v0.14555 MPO Zornitza Stark Mode of inheritance for gene: MPO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14554 MPO Zornitza Stark Classified gene: MPO as Amber List (moderate evidence)
Mendeliome v0.14554 MPO Zornitza Stark Gene: mpo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14553 MPO Zornitza Stark reviewed gene: MPO: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myeloperoxidase deficiency, MIM# 254600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14553 MPC1 Zornitza Stark Gene: mpc1 has been classified as Green List (High Evidence).
Mendeliome v0.14553 MPC1 Zornitza Stark Phenotypes for gene: MPC1 were changed from to Mitochondrial pyruvate carrier deficiency, MIM# 614741
Mendeliome v0.14552 MPC1 Zornitza Stark Publications for gene: MPC1 were set to
Mendeliome v0.14551 MPC1 Zornitza Stark Mode of inheritance for gene: MPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14550 MPC1 Zornitza Stark reviewed gene: MPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22628558, 34873722; Phenotypes: Mitochondrial pyruvate carrier deficiency, MIM# 614741; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14550 MOG Zornitza Stark Gene: mog has been classified as Red List (Low Evidence).
Mendeliome v0.14550 MOG Zornitza Stark Phenotypes for gene: MOG were changed from to Narcolepsy 7 , MIM# 614250
Mendeliome v0.14549 MOG Zornitza Stark Publications for gene: MOG were set to
Mendeliome v0.14548 MOG Zornitza Stark Mode of inheritance for gene: MOG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14547 MOG Zornitza Stark Classified gene: MOG as Red List (low evidence)
Mendeliome v0.14547 MOG Zornitza Stark Gene: mog has been classified as Red List (Low Evidence).
Mendeliome v0.14546 MOG Zornitza Stark reviewed gene: MOG: Rating: RED; Mode of pathogenicity: None; Publications: 21907016; Phenotypes: Narcolepsy 7 , MIM# 614250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14546 MOCS3 Zornitza Stark Gene: mocs3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14546 MOCS3 Zornitza Stark Phenotypes for gene: MOCS3 were changed from to Molybdenum cofactor deficiency MONDO:0020480
Mendeliome v0.14545 MOCS3 Zornitza Stark Publications for gene: MOCS3 were set to
Mendeliome v0.14544 MOCS3 Zornitza Stark Mode of inheritance for gene: MOCS3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14543 MOCS3 Zornitza Stark Classified gene: MOCS3 as Amber List (moderate evidence)
Mendeliome v0.14543 MOCS3 Zornitza Stark Gene: mocs3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14542 MOCS3 Zornitza Stark reviewed gene: MOCS3: Rating: AMBER; Mode of pathogenicity: None; Publications: 33897766, 28544736; Phenotypes: Molybdenum cofactor deficiency MONDO:0020480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14542 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Green List (High Evidence).
Mendeliome v0.14542 MOCS1 Zornitza Stark Publications for gene: MOCS1 were set to 21031595; 9921896; 12754701
Mendeliome v0.14541 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
Mendeliome v0.14541 MNX1 Zornitza Stark Phenotypes for gene: MNX1 were changed from to Currarino syndrome, MIM# 176450
Mendeliome v0.14540 MNX1 Zornitza Stark Publications for gene: MNX1 were set to
Mendeliome v0.14539 MNX1 Zornitza Stark Mode of inheritance for gene: MNX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14538 MMP2 Zornitza Stark Gene: mmp2 has been classified as Green List (High Evidence).
Mendeliome v0.14538 MMP2 Zornitza Stark Phenotypes for gene: MMP2 were changed from to Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600
Mendeliome v0.14537 MMP2 Zornitza Stark Publications for gene: MMP2 were set to
Mendeliome v0.14536 MMP2 Zornitza Stark Mode of inheritance for gene: MMP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14535 MMP2 Zornitza Stark reviewed gene: MMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431697, 15691365, 17059372, 17400654; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy, MIM# 259600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14535 ATP6V1A Elena Savva Publications for gene: ATP6V1A were set to 29668857; 28065471; 33320377
Mendeliome v0.14534 ATP6V1A Elena Savva Mode of inheritance for gene: ATP6V1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14533 ATP6V1A Elena Savva Publications for gene: ATP6V1A were set to
Mendeliome v0.14533 ATP6V1A Elena Savva Mode of inheritance for gene: ATP6V1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14533 ATP6V1A Elena Savva Marked gene: ATP6V1A as ready
Mendeliome v0.14533 ATP6V1A Elena Savva Gene: atp6v1a has been classified as Green List (High Evidence).
Mendeliome v0.14533 ATP6V1A Elena Savva Phenotypes for gene: ATP6V1A were changed from to Cutis laxa, autosomal recessive, type IID MIM#617403; Developmental and epileptic encephalopathy 93 MIM#618012
Mendeliome v0.14532 ATP6V1A Elena Savva reviewed gene: ATP6V1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29668857, 28065471, 33320377; Phenotypes: Cutis laxa, autosomal recessive, type IID MIM#617403, Developmental and epileptic encephalopathy 93 MIM#618012; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14532 ATP6AP2 Elena Savva Phenotypes for gene: ATP6AP2 were changed from ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423 to ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423
Mendeliome v0.14531 ATP6AP2 Elena Savva Marked gene: ATP6AP2 as ready
Mendeliome v0.14531 ATP6AP2 Elena Savva Gene: atp6ap2 has been classified as Green List (High Evidence).
Mendeliome v0.14531 ATP6AP2 Elena Savva Phenotypes for gene: ATP6AP2 were changed from to ?Parkinsonism with spasticity, X-linked MIM#300911; Congenital disorder of glycosylation, type IIr MIM#301045; Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423
Mendeliome v0.14531 ATP6AP2 Elena Savva Publications for gene: ATP6AP2 were set to
Mendeliome v0.14531 ATP6AP2 Elena Savva Mode of inheritance for gene: ATP6AP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14531 ATP6AP2 Elena Savva Mode of pathogenicity for gene: ATP6AP2 was changed from to Other
Mendeliome v0.14530 ATP6AP2 Elena Savva reviewed gene: ATP6AP2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 23595882; Phenotypes: ?Parkinsonism with spasticity, X-linked MIM#300911, Congenital disorder of glycosylation, type IIr MIM#301045, Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14530 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Mendeliome v0.14530 MMADHC Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism
Mendeliome v0.14529 MMADHC Zornitza Stark Publications for gene: MMADHC were set to
Mendeliome v0.14528 MMADHC Zornitza Stark Mode of inheritance for gene: MMADHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14527 MMACHC Zornitza Stark Gene: mmachc has been classified as Green List (High Evidence).
Mendeliome v0.14527 MMACHC Zornitza Stark Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type MIM#277400; Disorders of cobalamin absorption, transport and metabolism
Mendeliome v0.14526 MMACHC Zornitza Stark Publications for gene: MMACHC were set to
Mendeliome v0.14525 MMACHC Zornitza Stark Mode of inheritance for gene: MMACHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14524 MMAB Zornitza Stark Gene: mmab has been classified as Green List (High Evidence).
Mendeliome v0.14524 MMAB Zornitza Stark Phenotypes for gene: MMAB were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110
Mendeliome v0.14523 MMAB Zornitza Stark Mode of inheritance for gene: MMAB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14522 MMAB Zornitza Stark reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14522 MMAA Zornitza Stark Gene: mmaa has been classified as Green List (High Evidence).
Mendeliome v0.14522 MMAA Zornitza Stark Phenotypes for gene: MMAA were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100
Mendeliome v0.14521 MMAA Zornitza Stark Mode of inheritance for gene: MMAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14520 MMAA Zornitza Stark reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14520 MLPH Zornitza Stark Gene: mlph has been classified as Green List (High Evidence).
Mendeliome v0.14520 MLPH Zornitza Stark Phenotypes for gene: MLPH were changed from to Griscelli syndrome, type 3, MIM# 609227
Mendeliome v0.14519 MLPH Zornitza Stark Publications for gene: MLPH were set to
Mendeliome v0.14518 MLPH Zornitza Stark Mode of inheritance for gene: MLPH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14517 MLPH Zornitza Stark reviewed gene: MLPH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12897212, 32864751, 31721180; Phenotypes: Griscelli syndrome, type 3, MIM# 609227; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14517 MITF Zornitza Stark Marked gene: MITF as ready
Mendeliome v0.14517 MITF Zornitza Stark Gene: mitf has been classified as Green List (High Evidence).
Mendeliome v0.14517 MITF Zornitza Stark Phenotypes for gene: MITF were changed from to COMMAD syndrome, MIM# 617306; Tietz albinism-deafness syndrome, MIM# 103500; Waardenburg syndrome, type 2A, MIM# 193510
Mendeliome v0.14516 MITF Zornitza Stark Publications for gene: MITF were set to
Mendeliome v0.14515 MITF Zornitza Stark Mode of inheritance for gene: MITF was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14514 MITF Zornitza Stark reviewed gene: MITF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27889061, 32541011; Phenotypes: COMMAD syndrome, MIM# 617306, Tietz albinism-deafness syndrome, MIM# 103500, Waardenburg syndrome, type 2A, MIM# 193510; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14514 MIR936 Zornitza Stark Gene: mir936 has been classified as Red List (Low Evidence).
Mendeliome v0.14514 MIR936 Zornitza Stark Classified gene: MIR936 as Red List (low evidence)
Mendeliome v0.14514 MIR936 Zornitza Stark Gene: mir936 has been classified as Red List (Low Evidence).
Mendeliome v0.14513 MIR936 Zornitza Stark reviewed gene: MIR936: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14513 MIR184 Zornitza Stark Gene: mir184 has been classified as Green List (High Evidence).
Mendeliome v0.14513 MIR184 Zornitza Stark Phenotypes for gene: MIR184 were changed from to EDICT syndrome, MIM# 614303
Mendeliome v0.14512 MIR184 Zornitza Stark Publications for gene: MIR184 were set to
Mendeliome v0.14511 MIR184 Zornitza Stark Mode of inheritance for gene: MIR184 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14510 MIR184 Zornitza Stark reviewed gene: MIR184: Rating: GREEN; Mode of pathogenicity: None; Publications: 21996275, 22131394, 25373792, 24138095; Phenotypes: EDICT syndrome, MIM# 614303; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14510 MIR183 Zornitza Stark Gene: mir183 has been classified as Red List (Low Evidence).
Mendeliome v0.14510 MIR183 Zornitza Stark Classified gene: MIR183 as Red List (low evidence)
Mendeliome v0.14510 MIR183 Zornitza Stark Gene: mir183 has been classified as Red List (Low Evidence).
Mendeliome v0.14509 MIR183 Zornitza Stark reviewed gene: MIR183: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14509 CPSF3 Zornitza Stark Phenotypes for gene: CPSF3 were changed from Neurodevelopmental disorder, CPSF3-related, MONDO:0700092 to Neurodevelopmental disorder with microcephaly, hypotonia, and seizures (NEDMHS), MIM#619876
Mendeliome v0.14508 CPSF3 Zornitza Stark reviewed gene: CPSF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and seizures (NEDMHS), MIM#619876; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14508 ATP2C1 Elena Savva Publications for gene: ATP2C1 were set to 28551824
Mendeliome v0.14508 ATP2C1 Elena Savva Phenotypes for gene: ATP2C1 were changed from Hailey-Hailey disease (MIM# 169600) to Hailey-Hailey disease (MIM#169600)
Mendeliome v0.14507 ATP2C1 Elena Savva Phenotypes for gene: ATP2C1 were changed from to Hailey-Hailey disease (MIM# 169600)
Mendeliome v0.14506 ATP2C1 Elena Savva Publications for gene: ATP2C1 were set to
Mendeliome v0.14506 ATP2C1 Elena Savva Marked gene: ATP2C1 as ready
Mendeliome v0.14506 ATP2C1 Elena Savva Gene: atp2c1 has been classified as Green List (High Evidence).
Mendeliome v0.14506 ATP2C1 Elena Savva Mode of inheritance for gene: ATP2C1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14505 ATP6V0A1 Elena Savva Marked gene: ATP6V0A1 as ready
Mendeliome v0.14505 ATP6V0A1 Elena Savva Gene: atp6v0a1 has been classified as Green List (High Evidence).
Mendeliome v0.14505 MIR182 Zornitza Stark Gene: mir182 has been classified as Red List (Low Evidence).
Mendeliome v0.14505 MIR182 Zornitza Stark Classified gene: MIR182 as Red List (low evidence)
Mendeliome v0.14505 MIR182 Zornitza Stark Gene: mir182 has been classified as Red List (Low Evidence).
Mendeliome v0.14504 MIR182 Zornitza Stark reviewed gene: MIR182: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14504 MIP Zornitza Stark Gene: mip has been classified as Green List (High Evidence).
Mendeliome v0.14504 MIP Zornitza Stark Phenotypes for gene: MIP were changed from to Cataract 15, multiple types, MIM# 615274
Mendeliome v0.14503 MIP Zornitza Stark Publications for gene: MIP were set to
Mendeliome v0.14502 MIP Zornitza Stark Mode of inheritance for gene: MIP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14501 MIP Zornitza Stark reviewed gene: MIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802646, 16564824, 33530927, 30214549; Phenotypes: Cataract 15, multiple types, MIM# 615274; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14501 MIF Zornitza Stark Gene: mif has been classified as Red List (Low Evidence).
Mendeliome v0.14501 MIF Zornitza Stark Mode of inheritance for gene: MIF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14500 MIF Zornitza Stark Phenotypes for gene: MIF were changed from to {Rheumatoid arthritis, systemic juvenile, susceptibility to}, MIM# 604302
Mendeliome v0.14499 MIF Zornitza Stark Classified gene: MIF as Red List (low evidence)
Mendeliome v0.14499 MIF Zornitza Stark Gene: mif has been classified as Red List (Low Evidence).
Mendeliome v0.14498 MIF Zornitza Stark reviewed gene: MIF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Rheumatoid arthritis, systemic juvenile, susceptibility to}, MIM# 604302; Mode of inheritance: None
Mendeliome v0.14498 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Mendeliome v0.14498 MGME1 Zornitza Stark Phenotypes for gene: MGME1 were changed from to Mitochondrial DNA depletion syndrome 11, MIM# 615084
Mendeliome v0.14497 MGME1 Zornitza Stark Publications for gene: MGME1 were set to
Mendeliome v0.14496 MGME1 Zornitza Stark Mode of inheritance for gene: MGME1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14495 MGME1 Zornitza Stark reviewed gene: MGME1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23313956, 29572490, 28711739; Phenotypes: Mitochondrial DNA depletion syndrome 11, MIM# 615084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14495 MFN2 Zornitza Stark Gene: mfn2 has been classified as Green List (High Evidence).
Mendeliome v0.14495 MFN2 Zornitza Stark Publications for gene: MFN2 were set to
Mendeliome v0.14494 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Mendeliome v0.14494 MFF Zornitza Stark Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Mendeliome v0.14493 MFF Zornitza Stark Publications for gene: MFF were set to
Mendeliome v0.14492 MFF Zornitza Stark Mode of inheritance for gene: MFF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14491 MFF Zornitza Stark reviewed gene: MFF: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499341, 26783368, 32181496]; Phenotypes: Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14491 METTL23 Zornitza Stark Marked gene: METTL23 as ready
Mendeliome v0.14491 METTL23 Zornitza Stark Gene: mettl23 has been classified as Green List (High Evidence).
Mendeliome v0.14491 METTL23 Zornitza Stark Phenotypes for gene: METTL23 were changed from to Intellectual developmental disorder, autosomal recessive 44, MIM# 615942
Mendeliome v0.14490 METTL23 Zornitza Stark Publications for gene: METTL23 were set to
Mendeliome v0.14489 METTL23 Zornitza Stark Mode of inheritance for gene: METTL23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14488 METTL23 Zornitza Stark reviewed gene: METTL23: Rating: GREEN; Mode of pathogenicity: None; Publications: 24501276, 24626631; Phenotypes: Intellectual developmental disorder, autosomal recessive 44, MIM# 615942; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14488 MET Zornitza Stark Marked gene: MET as ready
Mendeliome v0.14488 MET Zornitza Stark Gene: met has been classified as Green List (High Evidence).
Mendeliome v0.14488 MET Zornitza Stark Phenotypes for gene: MET were changed from to Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074; Papillary renal cell carcinoma MONDO:0017884
Mendeliome v0.14487 MET Zornitza Stark Mode of inheritance for gene: MET was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14486 MET Zornitza Stark edited their review of gene: MET: Changed phenotypes: Renal cell carcinoma, papillary, 1, familial and somatic, MIM# 605074, Papillary renal cell carcinoma MONDO:0017884
Mendeliome v0.14486 MET Zornitza Stark reviewed gene: MET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Papillary renal cell carcinoma MONDO:0017884; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14486 ATG16L1 Elena Savva Marked gene: ATG16L1 as ready
Mendeliome v0.14486 ATG16L1 Elena Savva Gene: atg16l1 has been classified as Red List (Low Evidence).
Mendeliome v0.14486 MERTK Zornitza Stark Marked gene: MERTK as ready
Mendeliome v0.14486 MERTK Zornitza Stark Gene: mertk has been classified as Green List (High Evidence).
Mendeliome v0.14486 MERTK Zornitza Stark Phenotypes for gene: MERTK were changed from to Retinitis pigmentosa 38, MIM# 613862
Mendeliome v0.14485 MERTK Zornitza Stark Publications for gene: MERTK were set to
Mendeliome v0.14484 MERTK Zornitza Stark Mode of inheritance for gene: MERTK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14483 MERTK Zornitza Stark reviewed gene: MERTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062461, 17301963, 20300561, 22180149; Phenotypes: Retinitis pigmentosa 38, MIM# 613862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14483 MEIS1 Zornitza Stark Gene: meis1 has been classified as Red List (Low Evidence).
Mendeliome v0.14483 MEIS1 Zornitza Stark Classified gene: MEIS1 as Red List (low evidence)
Mendeliome v0.14483 MEIS1 Zornitza Stark Gene: meis1 has been classified as Red List (Low Evidence).
Mendeliome v0.14482 MEIS1 Zornitza Stark reviewed gene: MEIS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14482 ATP1A1 Elena Savva Phenotypes for gene: ATP1A1 were changed from Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314 to Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314
Mendeliome v0.14481 ATP2A2 Elena Savva Marked gene: ATP2A2 as ready
Mendeliome v0.14481 ATP2A2 Elena Savva Gene: atp2a2 has been classified as Green List (High Evidence).
Mendeliome v0.14481 ATG16L1 Elena Savva Phenotypes for gene: ATG16L1 were changed from to {Inflammatory bowel disease (Crohn disease) 10} MIM#611081
Mendeliome v0.14480 ATG16L1 Elena Savva Publications for gene: ATG16L1 were set to
Mendeliome v0.14480 ATG16L1 Elena Savva Classified gene: ATG16L1 as Red List (low evidence)
Mendeliome v0.14480 ATG16L1 Elena Savva Gene: atg16l1 has been classified as Red List (Low Evidence).
Mendeliome v0.14479 ATL3 Elena Savva Phenotypes for gene: ATL3 were changed from Neuropathy, hereditary sensory, type IF, MIM# 615632 to Neuropathy, hereditary sensory, type IF, MIM# 615632
Mendeliome v0.14478 ATP2A2 Elena Savva Phenotypes for gene: ATP2A2 were changed from to Acrokeratosis verruciformis MIM#101900; Darier disease MIM#124200
Mendeliome v0.14477 ATP2A2 Elena Savva Publications for gene: ATP2A2 were set to
Mendeliome v0.14477 ATP2A2 Elena Savva Mode of inheritance for gene: ATP2A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14476 ATP1A1 Elena Savva Phenotypes for gene: ATP1A1 were changed from to Charcot-Marie-Tooth disease, axonal, type 2DD MIM#618036; Hypomagnesemia, seizures, and mental retardation 2 MIM#618314
Mendeliome v0.14475 ATP1A1 Elena Savva Marked gene: ATP1A1 as ready
Mendeliome v0.14475 ATP1A1 Elena Savva Gene: atp1a1 has been classified as Green List (High Evidence).
Mendeliome v0.14475 ATG16L1 Elena Savva reviewed gene: ATG16L1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 20602997; Phenotypes: {Inflammatory bowel disease (Crohn disease) 10} MIM#611081; Mode of inheritance: None
Mendeliome v0.14475 ATL3 Elena Savva Phenotypes for gene: ATL3 were changed from to Neuropathy, hereditary sensory, type IF, MIM# 615632
Mendeliome v0.14474 ATL3 Elena Savva Marked gene: ATL3 as ready
Mendeliome v0.14474 ATL3 Elena Savva Gene: atl3 has been classified as Green List (High Evidence).
Mendeliome v0.14474 ATP2A2 Elena Savva reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24336169; Phenotypes: Acrokeratosis verruciformis MIM#101900, Darier disease MIM#124200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14474 ATP1A1 Elena Savva Publications for gene: ATP1A1 were set to
Mendeliome v0.14474 ATP1A1 Elena Savva Mode of inheritance for gene: ATP1A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14473 ATL3 Elena Savva Publications for gene: ATL3 were set to
Mendeliome v0.14473 ATL3 Elena Savva Mode of inheritance for gene: ATL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14472 ATF1 Elena Savva Marked gene: ATF1 as ready
Mendeliome v0.14472 ATF1 Elena Savva Gene: atf1 has been classified as Red List (Low Evidence).
Mendeliome v0.14472 ATF1 Elena Savva Classified gene: ATF1 as Red List (low evidence)
Mendeliome v0.14472 ATF1 Elena Savva Gene: atf1 has been classified as Red List (Low Evidence).
Mendeliome v0.14471 MEIOB Zornitza Stark Gene: meiob has been classified as Green List (High Evidence).
Mendeliome v0.14471 ASPN Elena Savva Gene: aspn has been classified as Red List (Low Evidence).
Mendeliome v0.14471 MEGF8 Zornitza Stark Gene: megf8 has been classified as Green List (High Evidence).
Mendeliome v0.14471 MEGF8 Zornitza Stark Phenotypes for gene: MEGF8 were changed from to Carpenter syndrome, MIM#614976
Mendeliome v0.14470 MEGF8 Zornitza Stark Publications for gene: MEGF8 were set to
Mendeliome v0.14469 MEGF8 Zornitza Stark Mode of inheritance for gene: MEGF8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14468 MEGF8 Zornitza Stark reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063620; Phenotypes: Carpenter syndrome, MIM#614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14468 MEFV Zornitza Stark Gene: mefv has been classified as Green List (High Evidence).
Mendeliome v0.14468 ASPN Elena Savva Publications for gene: ASPN were set to
Mendeliome v0.14467 MEFV Zornitza Stark Phenotypes for gene: MEFV were changed from to Familial Mediterranean fever MIM# 249100
Mendeliome v0.14466 MEFV Zornitza Stark Mode of inheritance for gene: MEFV was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14465 MEFV Zornitza Stark reviewed gene: MEFV: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Familial Mediterranean fever MIM# 249100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14465 MED23 Zornitza Stark Gene: med23 has been classified as Green List (High Evidence).
Mendeliome v0.14465 MED23 Zornitza Stark Phenotypes for gene: MED23 were changed from to Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy, MIM# 614249
Mendeliome v0.14464 MED23 Zornitza Stark Publications for gene: MED23 were set to
Mendeliome v0.14463 MED23 Zornitza Stark Mode of inheritance for gene: MED23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14462 MED23 Zornitza Stark reviewed gene: MED23: Rating: GREEN; Mode of pathogenicity: None; Publications: 21868677, 25845469, 27311965, 30847200, 31164858; Phenotypes: Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy, MIM# 614249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14462 MED13 Zornitza Stark Gene: med13 has been classified as Green List (High Evidence).
Mendeliome v0.14462 MED13 Zornitza Stark Phenotypes for gene: MED13 were changed from to Intellectual developmental disorder, autosomal dominant 61, MIM# 618009
Mendeliome v0.14461 MED13 Zornitza Stark Publications for gene: MED13 were set to
Mendeliome v0.14460 MED13 Zornitza Stark Mode of inheritance for gene: MED13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14459 MED13 Zornitza Stark reviewed gene: MED13: Rating: GREEN; Mode of pathogenicity: None; Publications: 29740699; Phenotypes: Intellectual developmental disorder, autosomal dominant 61, MIM# 618009; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14459 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Mendeliome v0.14459 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Rett syndrome, MIM# 312750; Intellectual developmental disorder, X-linked, syndromic 13, MIM# 300055; Encephalopathy, neonatal severe, MIM# 300673
Mendeliome v0.14458 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Mendeliome v0.14457 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14456 MECP2 Zornitza Stark reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome, MIM# 312750, Intellectual developmental disorder, X-linked, syndromic 13, MIM# 300055, Encephalopathy, neonatal severe, MIM# 300673; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14456 MCM9 Zornitza Stark Gene: mcm9 has been classified as Green List (High Evidence).
Mendeliome v0.14456 MCM9 Zornitza Stark Phenotypes for gene: MCM9 were changed from to Ovarian dysgenesis 4, MIM# 616185
Mendeliome v0.14455 MCM9 Zornitza Stark Publications for gene: MCM9 were set to
Mendeliome v0.14454 MCM9 Zornitza Stark Mode of inheritance for gene: MCM9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14453 MCM9 Zornitza Stark reviewed gene: MCM9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480036, 26771056, 33538981, 33095795; Phenotypes: Ovarian dysgenesis 4, MIM# 616185; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14453 MCM8 Zornitza Stark Gene: mcm8 has been classified as Green List (High Evidence).
Mendeliome v0.14453 ASPN Elena Savva Phenotypes for gene: ASPN were changed from {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850 to {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850
Mendeliome v0.14453 ASPN Elena Savva Phenotypes for gene: ASPN were changed from to {Lumbar disc degeneration} MIM#603932; {Osteoarthritis susceptibility 3} MIM#607850
Mendeliome v0.14452 ASPN Elena Savva Classified gene: ASPN as Red List (low evidence)
Mendeliome v0.14452 ASPN Elena Savva Gene: aspn has been classified as Red List (Low Evidence).
Mendeliome v0.14451 ARV1 Elena Savva Gene: arv1 has been classified as Green List (High Evidence).
Mendeliome v0.14451 ASPN Elena Savva Mode of inheritance for gene: ASPN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14450 ARV1 Elena Savva Phenotypes for gene: ARV1 were changed from to DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 38 MIM#61720; Dilated cardiomyopathy
Mendeliome v0.14449 ARV1 Elena Savva Publications for gene: ARV1 were set to
Mendeliome v0.14449 ARV1 Elena Savva Mode of inheritance for gene: ARV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14448 MCM8 Zornitza Stark Phenotypes for gene: MCM8 were changed from to Premature ovarian failure 10, MIM# 612885
Mendeliome v0.14447 MCM8 Zornitza Stark Publications for gene: MCM8 were set to
Mendeliome v0.14446 MCM8 Zornitza Stark Mode of inheritance for gene: MCM8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14445 MCM8 Zornitza Stark reviewed gene: MCM8: Rating: GREEN; Mode of pathogenicity: None; Publications: 25437880, 25873734; Phenotypes: Premature ovarian failure 10, MIM# 612885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14445 MCM6 Zornitza Stark Gene: mcm6 has been classified as Red List (Low Evidence).
Mendeliome v0.14445 MCM6 Zornitza Stark Phenotypes for gene: MCM6 were changed from to Lactase persistence/nonpersistence 223100
Mendeliome v0.14444 MCM6 Zornitza Stark Mode of inheritance for gene: MCM6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14443 MCM6 Zornitza Stark Classified gene: MCM6 as Red List (low evidence)
Mendeliome v0.14443 MCM6 Zornitza Stark Gene: mcm6 has been classified as Red List (Low Evidence).
Mendeliome v0.14442 MCM6 Zornitza Stark reviewed gene: MCM6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lactase persistence/nonpersistence 223100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14442 OAS1 Zornitza Stark Phenotypes for gene: OAS1 were changed from Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Mendeliome v0.14441 OAS1 Zornitza Stark edited their review of gene: OAS1: Changed phenotypes: Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Mendeliome v0.14441 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Mendeliome v0.14441 MCEE Zornitza Stark Phenotypes for gene: MCEE were changed from to Methylmalonyl-CoA epimerase deficiency MIM#251120; Organic acidurias
Mendeliome v0.14440 MCEE Zornitza Stark Publications for gene: MCEE were set to
Mendeliome v0.14439 MCEE Zornitza Stark Mode of inheritance for gene: MCEE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14438 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Green List (High Evidence).
Mendeliome v0.14438 MCCC2 Zornitza Stark Phenotypes for gene: MCCC2 were changed from to 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Organic acidurias
Mendeliome v0.14437 MCCC2 Zornitza Stark Publications for gene: MCCC2 were set to
Mendeliome v0.14436 MCCC2 Zornitza Stark Mode of inheritance for gene: MCCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14435 MCCC2 Zornitza Stark reviewed gene: MCCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14435 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Green List (High Evidence).
Mendeliome v0.14435 MCCC1 Zornitza Stark Phenotypes for gene: MCCC1 were changed from to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Organic acidurias
Mendeliome v0.14434 MCCC1 Zornitza Stark Publications for gene: MCCC1 were set to
Mendeliome v0.14433 MCCC1 Zornitza Stark Mode of inheritance for gene: MCCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14432 MCCC1 Zornitza Stark reviewed gene: MCCC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14432 MC3R Zornitza Stark Gene: mc3r has been classified as Red List (Low Evidence).
Mendeliome v0.14432 MC3R Zornitza Stark Phenotypes for gene: MC3R were changed from to {Obesity, severe, susceptibility to, BMIQ9} 602025
Mendeliome v0.14431 MC3R Zornitza Stark Mode of inheritance for gene: MC3R was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14430 MC3R Zornitza Stark Classified gene: MC3R as Red List (low evidence)
Mendeliome v0.14430 MC3R Zornitza Stark Gene: mc3r has been classified as Red List (Low Evidence).
Mendeliome v0.14429 MC3R Zornitza Stark reviewed gene: MC3R: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Obesity, severe, susceptibility to, BMIQ9} 602025; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14429 MC2R Zornitza Stark Gene: mc2r has been classified as Green List (High Evidence).
Mendeliome v0.14429 MC2R Zornitza Stark Phenotypes for gene: MC2R were changed from to Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200
Mendeliome v0.14428 MC2R Zornitza Stark Publications for gene: MC2R were set to
Mendeliome v0.14427 MC2R Zornitza Stark Mode of inheritance for gene: MC2R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14426 MC2R Zornitza Stark reviewed gene: MC2R: Rating: GREEN; Mode of pathogenicity: None; Publications: 8094489, 8227361; Phenotypes: Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14426 MBL2 Zornitza Stark Gene: mbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.14426 MBL2 Zornitza Stark Mode of inheritance for gene: MBL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14425 MBL2 Zornitza Stark Mode of inheritance for gene: MBL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14424 MBL2 Zornitza Stark Phenotypes for gene: MBL2 were changed from to {Chronic infections, due to MBL deficiency} 614372
Mendeliome v0.14423 MBL2 Zornitza Stark Classified gene: MBL2 as Red List (low evidence)
Mendeliome v0.14423 MBL2 Zornitza Stark Gene: mbl2 has been classified as Red List (Low Evidence).
Mendeliome v0.14422 MBL2 Zornitza Stark reviewed gene: MBL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Chronic infections, due to MBL deficiency} 614372; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14422 MATR3 Zornitza Stark Marked gene: MATR3 as ready
Mendeliome v0.14422 MATR3 Zornitza Stark Gene: matr3 has been classified as Green List (High Evidence).
Mendeliome v0.14422 MATR3 Zornitza Stark Phenotypes for gene: MATR3 were changed from to Amyotrophic lateral sclerosis 21, MIM# 606070; Distal myopathy
Mendeliome v0.14421 MATR3 Zornitza Stark Publications for gene: MATR3 were set to
Mendeliome v0.14420 MATR3 Zornitza Stark Mode of inheritance for gene: MATR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14419 MATR3 Zornitza Stark reviewed gene: MATR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19344878, 24686783, 35205163, 34659085, 34173818, 26493020; Phenotypes: Amyotrophic lateral sclerosis 21, MIM# 606070, Distal myopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14419 MAP3K1 Zornitza Stark Gene: map3k1 has been classified as Green List (High Evidence).
Mendeliome v0.14419 MAP3K1 Zornitza Stark Phenotypes for gene: MAP3K1 were changed from to 46XY sex reversal 6 (MIM#613762)
Mendeliome v0.14418 MAP3K1 Zornitza Stark Publications for gene: MAP3K1 were set to
Mendeliome v0.14417 MAP3K1 Zornitza Stark Mode of inheritance for gene: MAP3K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14416 MAP3K1 Zornitza Stark reviewed gene: MAP3K1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129722, 32986312; Phenotypes: 46XY sex reversal 6 (MIM#613762); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14416 MAK Zornitza Stark Gene: mak has been classified as Green List (High Evidence).
Mendeliome v0.14416 MAK Zornitza Stark Phenotypes for gene: MAK were changed from to Retinitis pigmentosa 62, MIM# 614181
Mendeliome v0.14415 MAK Zornitza Stark Publications for gene: MAK were set to
Mendeliome v0.14414 MAK Zornitza Stark Mode of inheritance for gene: MAK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14413 MAK Zornitza Stark reviewed gene: MAK: Rating: GREEN; Mode of pathogenicity: None; Publications: 21825139, 21835304; Phenotypes: Retinitis pigmentosa 62, MIM# 614181; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14413 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
Mendeliome v0.14413 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Mendeliome v0.14413 MAGT1 Zornitza Stark Phenotypes for gene: MAGT1 were changed from to Congenital disorder of glycosylation, type Icc (MIM# 301031); Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Mendeliome v0.14412 MAGT1 Zornitza Stark Publications for gene: MAGT1 were set to
Mendeliome v0.14411 MAGT1 Zornitza Stark Mode of inheritance for gene: MAGT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14410 MAGT1 Zornitza Stark changed review comment from: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect

PMID: 31714901;
- 23 XMEN patients from 17 families
- glycoproteomic analysis on T cells from 3 patients with XMEN showed defective glycosylation; to: PMID: 31036665;
- 3 affecteds (males; 2x CDG and 1x XMEN)
- All 3 patients have an N-glycosylation defect

PMID: 31714901;
- 23 XMEN patients from 17 families
- glycoproteomic analysis on T cells from 3 patients with XMEN showed defective glycosylation

These likely represent a single disorder.
Mendeliome v0.14410 MAGT1 Zornitza Stark reviewed gene: MAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31036665, 31714901; Phenotypes: Congenital disorder of glycosylation, type Icc (MIM# 301031), Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14410 GREM1 Krithika Murali reviewed gene: GREM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 22561515, 26493165, 21128281, 29804199; Phenotypes: hereditary mixed polyposis syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14410 MNX1 Abhijit Kulkarni reviewed gene: MNX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32571425, 33836786 , 11528505; Phenotypes: Currarino syndrome, MIM# 176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14410 MSX1 Abhijit Kulkarni reviewed gene: MSX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33419968, 33708320, 32192766; Phenotypes: Witkop syndrome (Ectodermal Dysplasia) (MIM: 189500),Cleft Lip+/- Cleft Palate (Rofacial Cleft- MIM :608874), Oligodontia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14410 MAGI2 Zornitza Stark Gene: magi2 has been classified as Green List (High Evidence).
Mendeliome v0.14410 MAGI2 Zornitza Stark Phenotypes for gene: MAGI2 were changed from to Nephrotic syndrome, type 15, MIM# 617609
Mendeliome v0.14409 MAGI2 Zornitza Stark Publications for gene: MAGI2 were set to
Mendeliome v0.14408 MAGI2 Zornitza Stark Mode of inheritance for gene: MAGI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14407 MAGI2 Zornitza Stark reviewed gene: MAGI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27932480, 25108225, 25271328, 31171376, 31010479; Phenotypes: Nephrotic syndrome, type 15, MIM# 617609; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14407 MYO3A Zornitza Stark Gene: myo3a has been classified as Green List (High Evidence).
Mendeliome v0.14407 OPHN1 Zornitza Stark Gene: ophn1 has been classified as Green List (High Evidence).
Mendeliome v0.14407 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, MIM#300486
Mendeliome v0.14406 OPHN1 Zornitza Stark Publications for gene: OPHN1 were set to
Mendeliome v0.14405 OPHN1 Zornitza Stark Mode of inheritance for gene: OPHN1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14404 OPHN1 Zornitza Stark edited their review of gene: OPHN1: Changed publications: 20528889, 9582072, 12807966, 16221952
Mendeliome v0.14404 OPHN1 Zornitza Stark Deleted their comment
Mendeliome v0.14404 OPHN1 Zornitza Stark commented on gene: OPHN1: OPHN1 variants cause cerebellar hypoplasia and distinctive facial appearance, macrocephaly is a feature. At least 8 families reported.
Mendeliome v0.14404 PAH Zornitza Stark Gene: pah has been classified as Green List (High Evidence).
Mendeliome v0.14404 PAH Zornitza Stark Phenotypes for gene: PAH were changed from to Phenylketonuria MIM#261600; Disorders of phenylalanine or tyrosine metabolism
Mendeliome v0.14403 PAH Zornitza Stark Publications for gene: PAH were set to
Mendeliome v0.14402 PAH Zornitza Stark Mode of inheritance for gene: PAH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14401 PCDH12 Zornitza Stark Gene: pcdh12 has been classified as Green List (High Evidence).
Mendeliome v0.14401 PCDH12 Zornitza Stark Phenotypes for gene: PCDH12 were changed from to Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280
Mendeliome v0.14400 PCDH12 Zornitza Stark Publications for gene: PCDH12 were set to
Mendeliome v0.14399 PCDH12 Zornitza Stark Mode of inheritance for gene: PCDH12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14398 PCDH12 Zornitza Stark reviewed gene: PCDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27164683, 30178464; Phenotypes: Diencephalic-mesencephalic junction dysplasia syndrome 1, MIM# 251280; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14398 PEPD Zornitza Stark Gene: pepd has been classified as Green List (High Evidence).
Mendeliome v0.14398 PEPD Zornitza Stark Phenotypes for gene: PEPD were changed from to Prolidase deficiency MIM#170100; disorders of peptide metabolism
Mendeliome v0.14397 PEPD Zornitza Stark Publications for gene: PEPD were set to
Mendeliome v0.14396 PEPD Zornitza Stark Mode of inheritance for gene: PEPD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14395 PEX10 Zornitza Stark Gene: pex10 has been classified as Green List (High Evidence).
Mendeliome v0.14395 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from to Peroxisome biogenesis disorder 6A (Zellweger) (MIM#614870); Peroxisome biogenesis disorder 6B (MIM#614871)
Mendeliome v0.14394 PEX10 Zornitza Stark Publications for gene: PEX10 were set to
Mendeliome v0.14393 PEX10 Zornitza Stark Mode of inheritance for gene: PEX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14392 PCK1 Zornitza Stark Gene: pck1 has been classified as Green List (High Evidence).
Mendeliome v0.14392 PCK1 Zornitza Stark Phenotypes for gene: PCK1 were changed from to Phosphoenolpyruvate carboxykinase deficiency, cytosolic MIM#261680; Disorders of gluconeogenesis
Mendeliome v0.14391 PCK1 Zornitza Stark Publications for gene: PCK1 were set to
Mendeliome v0.14390 PCK1 Zornitza Stark Mode of inheritance for gene: PCK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14389 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Mendeliome v0.14389 REEP1 Zornitza Stark Gene: reep1 has been classified as Green List (High Evidence).
Mendeliome v0.14389 REEP1 Zornitza Stark Phenotypes for gene: REEP1 were changed from to Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy
Mendeliome v0.14388 REEP1 Zornitza Stark Publications for gene: REEP1 were set to
Mendeliome v0.14387 REEP1 Zornitza Stark Mode of inheritance for gene: REEP1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14386 RLBP1 Zornitza Stark Gene: rlbp1 has been classified as Green List (High Evidence).
Mendeliome v0.14386 RLBP1 Zornitza Stark Phenotypes for gene: RLBP1 were changed from to Fundus albipunctatus MIM#136880; Bothnia retinal dystrophy MIM#607475
Mendeliome v0.14385 RLBP1 Zornitza Stark Publications for gene: RLBP1 were set to
Mendeliome v0.14384 RLBP1 Zornitza Stark Mode of inheritance for gene: RLBP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14383 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Mendeliome v0.14383 RMND1 Zornitza Stark Phenotypes for gene: RMND1 were changed from to Combined oxidative phosphorylation deficiency 11 MIM#614922
Mendeliome v0.14382 RMND1 Zornitza Stark Mode of inheritance for gene: RMND1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14381 RBFOX2 Chern Lim Deleted their comment
Mendeliome v0.14381 RNASEH1 Zornitza Stark Gene: rnaseh1 has been classified as Green List (High Evidence).
Mendeliome v0.14381 RNASEH1 Zornitza Stark Phenotypes for gene: RNASEH1 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 MIM#616479
Mendeliome v0.14380 RNASEH1 Zornitza Stark Publications for gene: RNASEH1 were set to
Mendeliome v0.14379 RBFOX2 Chern Lim edited their review of gene: RBFOX2: Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; Changed publications: PMID: 26785492, 27670201, 27485310, 25205790, 35137168, 26785492
Mendeliome v0.14379 RNASEH1 Zornitza Stark Mode of inheritance for gene: RNASEH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14378 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Green List (High Evidence).
Mendeliome v0.14378 RNASEH2A Zornitza Stark Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4 MIM#610333
Mendeliome v0.14377 RNASEH2A Zornitza Stark Publications for gene: RNASEH2A were set to
Mendeliome v0.14376 RNASEH2A Zornitza Stark Mode of inheritance for gene: RNASEH2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14375 RNF139 Zornitza Stark Gene: rnf139 has been classified as Red List (Low Evidence).
Mendeliome v0.14375 RNF139 Zornitza Stark Phenotypes for gene: RNF139 were changed from to Renal cell carcinoma MIM#144700
Mendeliome v0.14374 RNF139 Zornitza Stark Publications for gene: RNF139 were set to
Mendeliome v0.14373 RNF139 Zornitza Stark Mode of inheritance for gene: RNF139 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14372 RNF139 Zornitza Stark Classified gene: RNF139 as Red List (low evidence)
Mendeliome v0.14372 RNF139 Zornitza Stark Gene: rnf139 has been classified as Red List (Low Evidence).
Mendeliome v0.14371 RP1 Zornitza Stark Gene: rp1 has been classified as Green List (High Evidence).
Mendeliome v0.14371 RP1 Zornitza Stark Phenotypes for gene: RP1 were changed from to Retinitis pigmentosa 1 MIM#180100
Mendeliome v0.14370 RP1 Zornitza Stark Publications for gene: RP1 were set to
Mendeliome v0.14369 RP1 Zornitza Stark Mode of inheritance for gene: RP1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14368 RP2 Zornitza Stark Gene: rp2 has been classified as Green List (High Evidence).
Mendeliome v0.14368 RP2 Zornitza Stark Phenotypes for gene: RP2 were changed from to Retinitis pigmentosa 2 MIM#312600
Mendeliome v0.14367 RP2 Zornitza Stark Publications for gene: RP2 were set to
Mendeliome v0.14366 RP2 Zornitza Stark Mode of inheritance for gene: RP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14365 RP9 Zornitza Stark Gene: rp9 has been classified as Red List (Low Evidence).
Mendeliome v0.14365 RP9 Zornitza Stark Phenotypes for gene: RP9 were changed from to Retinitis pigmentosa 9 MIM#180104
Mendeliome v0.14364 RP9 Zornitza Stark Publications for gene: RP9 were set to
Mendeliome v0.14363 RP9 Zornitza Stark Mode of inheritance for gene: RP9 was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14362 RP9 Zornitza Stark Mode of inheritance for gene: RP9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Mendeliome v0.14361 RP9 Zornitza Stark Classified gene: RP9 as Red List (low evidence)
Mendeliome v0.14361 RP9 Zornitza Stark Gene: rp9 has been classified as Red List (Low Evidence).
Mendeliome v0.14360 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Mendeliome v0.14360 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from to {Malignant hyperthermia susceptibility 1} MIM#145600; Central core disease, MIM# 117000; King-Denborough syndrome , MIM#619542; Minicore myopathy with external ophthalmoplegia , MIM#255320; Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000
Mendeliome v0.14359 RYR1 Zornitza Stark Publications for gene: RYR1 were set to
Mendeliome v0.14358 RYR1 Zornitza Stark Mode of inheritance for gene: RYR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14357 RYR1 Zornitza Stark reviewed gene: RYR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Central core disease, MIM# 117000, King-Denborough syndrome , MIM#619542, Minicore myopathy with external ophthalmoplegia , MIM#255320, Neuromuscular disease, congenital, with uniform type 1 fiber, MIM# 117000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14357 SACS Zornitza Stark Gene: sacs has been classified as Green List (High Evidence).
Mendeliome v0.14357 SACS Zornitza Stark Phenotypes for gene: SACS were changed from to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Mendeliome v0.14356 SACS Zornitza Stark Mode of inheritance for gene: SACS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14355 SACS Zornitza Stark Tag SV/CNV tag was added to gene: SACS.
Mendeliome v0.14355 SCN11A Zornitza Stark Gene: scn11a has been classified as Green List (High Evidence).
Mendeliome v0.14355 SCN11A Zornitza Stark Phenotypes for gene: SCN11A were changed from to Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548; Episodic pain syndrome, familial, 3, MIM# 615552
Mendeliome v0.14354 SCN11A Zornitza Stark Publications for gene: SCN11A were set to
Mendeliome v0.14353 SCN11A Zornitza Stark Mode of inheritance for gene: SCN11A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14352 SCN11A Zornitza Stark edited their review of gene: SCN11A: Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type VII, MIM# 615548, Episodic pain syndrome, familial, 3, MIM# 615552
Mendeliome v0.14352 TMC8 Zornitza Stark Marked gene: TMC8 as ready
Mendeliome v0.14352 TMC8 Zornitza Stark Gene: tmc8 has been classified as Green List (High Evidence).
Mendeliome v0.14352 TMC8 Zornitza Stark Phenotypes for gene: TMC8 were changed from to Epidermodysplasia verruciformis 2, MIM# 618231
Mendeliome v0.14351 TMC8 Zornitza Stark Publications for gene: TMC8 were set to
Mendeliome v0.14350 TMC8 Zornitza Stark Mode of inheritance for gene: TMC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14349 TMC8 Zornitza Stark reviewed gene: TMC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 12426567, 28646613; Phenotypes: Epidermodysplasia verruciformis 2, MIM# 618231; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14349 ATP6V0A1 Bryony Thompson Mode of inheritance for gene: ATP6V0A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14348 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Green List (high evidence)
Mendeliome v0.14348 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Green List (High Evidence).
Mendeliome v0.14347 ATP6V0A1 Bryony Thompson Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Mendeliome v0.14346 ATP6V0A1 Bryony Thompson Phenotypes for gene: ATP6V0A1 were changed from Developmental disorder; Rett syndrome-like to Neurodevelopmental disorder MONDO:0700092, ATP6V0A1-associated
Mendeliome v0.14345 RLBP1 Belinda Chong reviewed gene: RLBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9326942, 11453974, 11868161, 21447491, 25429852, 14718298; Phenotypes: Fundus albipunctatus MIM#136880, Bothnia retinal dystrophy MIM#607475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14345 RBFOX2 Chern Lim gene: RBFOX2 was added
gene: RBFOX2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RBFOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX2 were set to PMID: 26785492; 27670201; 27485310; 25205790; 35137168
Phenotypes for gene: RBFOX2 were set to Hypoplastic left heart syndrome (HLHS)
Review for gene: RBFOX2 was set to AMBER
gene: RBFOX2 was marked as current diagnostic
Added comment: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS).
No further patient-specific clinical or variant info were available.

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Sources: Literature
Mendeliome v0.14345 ATF1 Abhijit Kulkarni reviewed gene: ATF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14345 GRIA4 Ain Roesley Gene: gria4 has been classified as Green List (High Evidence).
Mendeliome v0.14345 GRIA4 Ain Roesley Phenotypes for gene: GRIA4 were changed from to Neurodevelopmental disorder with or without seizures and gait abnormalities MIM#617864
Mendeliome v0.14345 GRIA4 Ain Roesley Publications for gene: GRIA4 were set to
Mendeliome v0.14345 GRIA4 Ain Roesley Mode of inheritance for gene: GRIA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14344 GRIA4 Ain Roesley reviewed gene: GRIA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 35518358, 29220673; Phenotypes: Neurodevelopmental disorder with or without seizures and gait abnormalities MIM#617864; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.14344 GRID2 Ain Roesley Gene: grid2 has been classified as Green List (High Evidence).
Mendeliome v0.14344 GRID2 Ain Roesley Phenotypes for gene: GRID2 were changed from to Spinocerebellar ataxia, autosomal recessive 18 MIM#616204
Mendeliome v0.14344 GRID2 Ain Roesley Publications for gene: GRID2 were set to
Mendeliome v0.14343 GRID2 Ain Roesley Tag SV/CNV tag was added to gene: GRID2.
Mendeliome v0.14343 GRID2 Ain Roesley reviewed gene: GRID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32622959, 32170608; Phenotypes: Spinocerebellar ataxia, autosomal recessive 18 MIM#616204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14343 GRIN2D Ain Roesley Gene: grin2d has been classified as Green List (High Evidence).
Mendeliome v0.14343 GRIN2D Ain Roesley Phenotypes for gene: GRIN2D were changed from to Developmental and epileptic encephalopathy 46 MIM#617162
Mendeliome v0.14342 GRIN2D Ain Roesley Publications for gene: GRIN2D were set to
Mendeliome v0.14342 GRIN2D Ain Roesley Mode of inheritance for gene: GRIN2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14341 GRIN2D Ain Roesley reviewed gene: GRIN2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616483, 30280376; Phenotypes: Developmental and epileptic encephalopathy 46 617162; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.14341 ASPN Abhijit Kulkarni reviewed gene: ASPN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 25689697; Mode of inheritance: None
Mendeliome v0.14341 TMC8 Abhijit Kulkarni reviewed gene: TMC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 34459021, 28646613; Phenotypes: Epidermodysplasia verruciformis 2 (MIM: 61831); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14341 BICC1 Abhijit Kulkarni reviewed gene: BICC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: renal dysplasia, cystic, susceptibility to; Mode of inheritance: None
Mendeliome v0.14341 ARV1 Abhijit Kulkarni reviewed gene: ARV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35227294, 27270415, 25558065; Phenotypes: DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 38 ( MIM:61720) Dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14341 RMND1 Belinda Chong reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14341 UGT1A1 Zornitza Stark Marked gene: UGT1A1 as ready
Mendeliome v0.14341 UGT1A1 Zornitza Stark Gene: ugt1a1 has been classified as Green List (High Evidence).
Mendeliome v0.14341 UGT1A1 Zornitza Stark Phenotypes for gene: UGT1A1 were changed from to Bilirubin UDP-glucuronosyltransferase 1 deficiency (Disorders of bile acid metabolism and transport); Crigler-Najjar syndrome, type I 218800; Crigler-Najjar syndrome, type II 606785
Mendeliome v0.14340 UGT1A1 Zornitza Stark Mode of inheritance for gene: UGT1A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14339 UNC13D Zornitza Stark Gene: unc13d has been classified as Green List (High Evidence).
Mendeliome v0.14339 UNG Zornitza Stark Gene: ung has been classified as Green List (High Evidence).
Mendeliome v0.14339 UNG Zornitza Stark Phenotypes for gene: UNG were changed from to Immunodeficiency with hyper IgM, type 5, MIM#608106
Mendeliome v0.14338 UNG Zornitza Stark Publications for gene: UNG were set to
Mendeliome v0.14337 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Green List (High Evidence).
Mendeliome v0.14337 UQCC2 Zornitza Stark Phenotypes for gene: UQCC2 were changed from to Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824
Mendeliome v0.14336 UQCC2 Zornitza Stark Publications for gene: UQCC2 were set to
Mendeliome v0.14335 UQCC2 Zornitza Stark Mode of inheritance for gene: UQCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14334 UQCRB Zornitza Stark Gene: uqcrb has been classified as Green List (High Evidence).
Mendeliome v0.14334 UQCRB Zornitza Stark Phenotypes for gene: UQCRB were changed from to Mitochondrial complex III deficiency, nuclear type 3, MIM# 615158
Mendeliome v0.14333 UQCRB Zornitza Stark Publications for gene: UQCRB were set to
Mendeliome v0.14332 UQCRB Zornitza Stark Mode of inheritance for gene: UQCRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14331 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Mendeliome v0.14331 UROD Zornitza Stark Phenotypes for gene: UROD were changed from to Porphyria cutanea tarda; Porphyria, hepatoerythropoietic (MIM#176100)
Mendeliome v0.14330 UROD Zornitza Stark Publications for gene: UROD were set to
Mendeliome v0.14329 UROD Zornitza Stark Mode of inheritance for gene: UROD was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14328 MAGED2 Zornitza Stark Gene: maged2 has been classified as Green List (High Evidence).
Mendeliome v0.14328 MAGED2 Zornitza Stark Phenotypes for gene: MAGED2 were changed from to Bartter syndrome, type 5, antenatal, transient, MIM# 300971
Mendeliome v0.14327 MAGED2 Zornitza Stark Publications for gene: MAGED2 were set to
Mendeliome v0.14326 MAGED2 Zornitza Stark Mode of inheritance for gene: MAGED2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14325 MAGED2 Zornitza Stark reviewed gene: MAGED2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120771; Phenotypes: Bartter syndrome, type 5, antenatal, transient, MIM# 300971; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14325 MRPS2 Zornitza Stark Gene: mrps2 has been classified as Green List (High Evidence).
Mendeliome v0.14325 MRPS2 Zornitza Stark Phenotypes for gene: MRPS2 were changed from to Combined oxidative phosphorylation deficiency 36, MIM# 617950
Mendeliome v0.14324 MRPS2 Zornitza Stark Publications for gene: MRPS2 were set to
Mendeliome v0.14323 MRPS2 Zornitza Stark Mode of inheritance for gene: MRPS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14322 MRPS2 Zornitza Stark reviewed gene: MRPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29576219, 34991560; Phenotypes: Combined oxidative phosphorylation deficiency 36, MIM# 617950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14322 MSH3 Zornitza Stark Gene: msh3 has been classified as Green List (High Evidence).
Mendeliome v0.14322 MSH3 Zornitza Stark Phenotypes for gene: MSH3 were changed from to Familial adenomatous polyposis 4 , MIM#617100
Mendeliome v0.14321 MSH3 Zornitza Stark Publications for gene: MSH3 were set to
Mendeliome v0.14320 MSH3 Zornitza Stark Mode of inheritance for gene: MSH3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14319 MSH3 Zornitza Stark reviewed gene: MSH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476653, 10706084, 34843512; Phenotypes: Familial adenomatous polyposis 4 , MIM#617100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14319 MSRB3 Zornitza Stark Gene: msrb3 has been classified as Green List (High Evidence).
Mendeliome v0.14319 MSRB3 Zornitza Stark Phenotypes for gene: MSRB3 were changed from to Deafness, autosomal recessive 74, MIM# 613718
Mendeliome v0.14318 MSRB3 Zornitza Stark Publications for gene: MSRB3 were set to
Mendeliome v0.14317 MSRB3 Zornitza Stark Mode of inheritance for gene: MSRB3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14316 MSRB3 Zornitza Stark reviewed gene: MSRB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19650862, 24191262, 21185009; Phenotypes: Deafness, autosomal recessive 74, MIM# 613718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14316 MTAP Zornitza Stark Marked gene: MTAP as ready
Mendeliome v0.14316 MTAP Zornitza Stark Gene: mtap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14316 MTAP Zornitza Stark Phenotypes for gene: MTAP were changed from to Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250
Mendeliome v0.14315 MTAP Zornitza Stark Publications for gene: MTAP were set to
Mendeliome v0.14314 MTAP Zornitza Stark Mode of inheritance for gene: MTAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14313 MTAP Zornitza Stark Classified gene: MTAP as Amber List (moderate evidence)
Mendeliome v0.14313 MTAP Zornitza Stark Gene: mtap has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14312 MTAP Zornitza Stark reviewed gene: MTAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 22464254; Phenotypes: Diaphyseal medullary stenosis with malignant fibrous histiocytoma, MIM# 112250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14312 MTFMT Zornitza Stark Marked gene: MTFMT as ready
Mendeliome v0.14312 MTFMT Zornitza Stark Gene: mtfmt has been classified as Green List (High Evidence).
Mendeliome v0.14312 MTFMT Zornitza Stark Phenotypes for gene: MTFMT were changed from to Combined oxidative phosphorylation deficiency 15, MIM# 614947; Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248
Mendeliome v0.14311 MTFMT Zornitza Stark Publications for gene: MTFMT were set to
Mendeliome v0.14310 MTFMT Zornitza Stark Mode of inheritance for gene: MTFMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14309 MTFMT Zornitza Stark reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907147, 23499752, 24461907, 22499348; Phenotypes: Combined oxidative phosphorylation deficiency 15, MIM# 614947, Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14309 MTHFD1 Zornitza Stark Marked gene: MTHFD1 as ready
Mendeliome v0.14309 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
Mendeliome v0.14309 MTHFD1 Zornitza Stark Publications for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
Mendeliome v0.14308 MTHFD1 Zornitza Stark Phenotypes for gene: MTHFD1 were changed from to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
Mendeliome v0.14307 MTHFD1 Zornitza Stark Publications for gene: MTHFD1 were set to
Mendeliome v0.14306 MTHFD1 Zornitza Stark Mode of inheritance for gene: MTHFD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14305 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Mendeliome v0.14305 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Mendeliome v0.14305 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250; Disorders of folate metabolism and transport
Mendeliome v0.14304 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Mendeliome v0.14303 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14302 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Mendeliome v0.14302 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Mendeliome v0.14302 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from to Myopathy, centronuclear, X-linked, MIM# 310400
Mendeliome v0.14301 MTM1 Zornitza Stark Publications for gene: MTM1 were set to
Mendeliome v0.14300 MTM1 Zornitza Stark Mode of inheritance for gene: MTM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14299 MTM1 Zornitza Stark reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10790201; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14299 MTO1 Zornitza Stark Marked gene: MTO1 as ready
Mendeliome v0.14299 MTO1 Zornitza Stark Gene: mto1 has been classified as Green List (High Evidence).
Mendeliome v0.14299 MTO1 Zornitza Stark Phenotypes for gene: MTO1 were changed from to Combined oxidative phosphorylation deficiency 10, OMIM #614702
Mendeliome v0.14298 MTO1 Zornitza Stark Publications for gene: MTO1 were set to
Mendeliome v0.14297 MTO1 Zornitza Stark Mode of inheritance for gene: MTO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14296 MTO1 Zornitza Stark reviewed gene: MTO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26061759, 29331171, 23929671; Phenotypes: Combined oxidative phosphorylation deficiency 10, OMIM #614702; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14296 MTOR Zornitza Stark Mode of pathogenicity for gene: MTOR was changed from to Other
Mendeliome v0.14295 MTOR Zornitza Stark Marked gene: MTOR as ready
Mendeliome v0.14295 MTOR Zornitza Stark Gene: mtor has been classified as Green List (High Evidence).
Mendeliome v0.14295 MTOR Zornitza Stark Phenotypes for gene: MTOR were changed from to Smith-Kingsmore syndrome, MIM# 616638; Focal cortical dysplasia, type II, somatic, MIM# 607341; Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283
Mendeliome v0.14294 MTOR Zornitza Stark Publications for gene: MTOR were set to
Mendeliome v0.14293 MTOR Zornitza Stark Mode of inheritance for gene: MTOR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14292 MTOR Zornitza Stark reviewed gene: MTOR: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28892148, 25878179, 26018084; Phenotypes: Smith-Kingsmore syndrome, MIM# 616638, Focal cortical dysplasia, type II, somatic, MIM# 607341, Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, MONDO:0100283; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14292 TXNDC15 Zornitza Stark Phenotypes for gene: TXNDC15 were changed from Meckel-Gruber syndrome to Meckel syndrome 14, MIM# 619879
Mendeliome v0.14291 TXNDC15 Zornitza Stark edited their review of gene: TXNDC15: Changed phenotypes: Meckel syndrome 14, MIM# 619879
Mendeliome v0.14291 DNASE1 Krithika Murali reviewed gene: DNASE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Systemic lupus erythematosus, susceptibility to} - MIM#152700; Mode of inheritance: None
Mendeliome v0.14291 DNAJC6 Krithika Murali reviewed gene: DNAJC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22563501, 23211418, 26528954; Phenotypes: Parkinson disease 19a, juvenile-onset - MIM#615528, Parkinson disease 19b, early-onset - MIM#615528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14291 DNAJC5 Krithika Murali reviewed gene: DNAJC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22978711, 21820099, 22235333, 31919451, 26659577; Phenotypes: Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant - MIM#162350, ceroid lipofuscinosis, neuronal, 4 (Kufs type) - MONDO:0008083; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14291 DNAJC3 Krithika Murali changed review comment from: Well-established association with monogenic diabetes with growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families).; to: Well-established association with monogenic diabetes. Growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported in affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families).
Mendeliome v0.14291 DNAJC3 Krithika Murali reviewed gene: DNAJC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33486469, 34630333, 34654017, 32738013; Phenotypes: ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus - MIM#616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14291 DNAJC21 Krithika Murali reviewed gene: DNAJC21: Rating: GREEN; Mode of pathogenicity: None; Publications: 29700810, 28062395, 27346687; Phenotypes: Bone marrow failure syndrome 3 - MIM#617052; Mode of inheritance: None
Mendeliome v0.14291 DNASE1L3 Krithika Murali reviewed gene: DNASE1L3: Rating: ; Mode of pathogenicity: None; Publications: 30008451, 22019780, 27821515; Phenotypes: Systemic lupus erythematosus 16 - MIM#614420; Mode of inheritance: None
Mendeliome v0.14291 DNM1L Krithika Murali reviewed gene: DNM1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - MIM#614388 (AD, AR), Optic atrophy 5 - MIM#610708 (AD); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14291 DPY19L2 Krithika Murali reviewed gene: DPY19L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 9 - MIM#613958; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14291 DRAM2 Krithika Murali reviewed gene: DRAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25983245, 29555955, 31394102; Phenotypes: Cone-rod dystrophy 21 - MIM#616502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14291 DRD2 Krithika Murali reviewed gene: DRD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14291 DRD3 Krithika Murali reviewed gene: DRD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Essential tremor, hereditary, 1} - MIM#190300, {Schizophrenia, susceptibility to} - MIM#181500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14291 DSCAM Krithika Murali Deleted their comment
Mendeliome v0.14291 DSCAM Krithika Murali edited their review of gene: DSCAM: Added comment: No OMIM gene disease association. Variants predominantly identified from large cohort studies with limited phenotypic information. Associations with ID, ASD, Hirschsprung disease reported. One homozygous splice site variant reported with no parental phenotypes provided.

PMID 34253863 Lim et al 2021 - 12 yo proband with severe autism spectrum disorder diagnosed age 3, de novo heterozygous c.2051 del p.(L684X) variant identified (absent from gnomAD). Skin fibroblast human iPSC cells generated from proband and healthy controls. Forebrain-like induced neuronal cells showed reduced mRNA expression for NMDA-R subunits.

PMID 28600779 Monies et al 2017 - Homozygous splice site variant identified in proband from consanguineous Saudi family. Proband had growth restriction, microcephaly, developmental delay. Parental phenotype not provided.

PMID 30095639 and PMID 23671607 - report association between DSCAM polymorphisms and Hirschsprung disease in Chinese and European populations.

PMID 27824329 Wang et al 2016 - 2 denovo mutations in mixed ID/ASD cohort of 1,045; including comparison of previously published cases 6 LOF out of 4,998 cases.

PMID 28191889 2 denovo LOF in 13,407 mixed ID/ASD cases plus 4 previosly published cases our ot 6158; conclude denovo LOF enriched in cases vs controls

PMID 21904980; mouse model – het LOF mice show hydrocephalus, decreased motor function and impaired motor learning ability,

Evidence for missense lacking currently; Changed publications: 34253863, 32807774, 28600779, 21904980, 28191889, 27824329, 30095639, 23671607
Mendeliome v0.14291 DSCAM Krithika Murali reviewed gene: DSCAM: Rating: AMBER; Mode of pathogenicity: None; Publications: 34253863, 32807774, 28600779; Phenotypes: Autism, ID; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14291 MTTP Zornitza Stark Marked gene: MTTP as ready
Mendeliome v0.14291 MTTP Zornitza Stark Gene: mttp has been classified as Green List (High Evidence).
Mendeliome v0.14291 MTTP Zornitza Stark Phenotypes for gene: MTTP were changed from to Abetalipoproteinaemia, MIM# 200100
Mendeliome v0.14290 MTTP Zornitza Stark Publications for gene: MTTP were set to
Mendeliome v0.14289 MTTP Zornitza Stark Mode of inheritance for gene: MTTP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14288 MTTP Zornitza Stark reviewed gene: MTTP: Rating: GREEN; Mode of pathogenicity: None; Publications: 17275380, 34078172, 34052173, 33258201; Phenotypes: Abetalipoproteinaemia, MIM# 200100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14288 MUT Zornitza Stark Marked gene: MUT as ready
Mendeliome v0.14288 MUT Zornitza Stark Gene: mut has been classified as Green List (High Evidence).
Mendeliome v0.14288 MUT Zornitza Stark Phenotypes for gene: MUT were changed from to Methylmalonic aciduria, mut(0) type, MIM# 251000
Mendeliome v0.14287 MUT Zornitza Stark Publications for gene: MUT were set to
Mendeliome v0.14286 MUT Zornitza Stark Mode of inheritance for gene: MUT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14285 MUT Zornitza Stark reviewed gene: MUT: Rating: GREEN; Mode of pathogenicity: None; Publications: 1977311, 11528502, 12948746; Phenotypes: Methylmalonic aciduria, mut(0) type, MIM# 251000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14285 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Mendeliome v0.14285 MVK Zornitza Stark Phenotypes for gene: MVK were changed from to Mevalonic aciduria MIM# 610377
Mendeliome v0.14284 MVK Zornitza Stark Publications for gene: MVK were set to
Mendeliome v0.14283 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14282 MVK Zornitza Stark reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mevalonic aciduria MIM#610377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14282 MXI1 Zornitza Stark Gene: mxi1 has been classified as Red List (Low Evidence).
Mendeliome v0.14282 MXI1 Zornitza Stark Classified gene: MXI1 as Red List (low evidence)
Mendeliome v0.14282 MXI1 Zornitza Stark Gene: mxi1 has been classified as Red List (Low Evidence).
Mendeliome v0.14281 MXI1 Zornitza Stark reviewed gene: MXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14281 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
Mendeliome v0.14281 MYD88 Zornitza Stark Phenotypes for gene: MYD88 were changed from to Immunodeficiency 68, MIM# 612260
Mendeliome v0.14280 MYD88 Zornitza Stark Publications for gene: MYD88 were set to
Mendeliome v0.14279 MYD88 Zornitza Stark Mode of inheritance for gene: MYD88 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14278 MYD88 Zornitza Stark reviewed gene: MYD88: Rating: GREEN; Mode of pathogenicity: None; Publications: 18669862, 20538326, 31301515; Phenotypes: Immunodeficiency 68, MIM# 612260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14278 MYH14 Zornitza Stark Gene: myh14 has been classified as Green List (High Evidence).
Mendeliome v0.14278 MYH14 Zornitza Stark Phenotypes for gene: MYH14 were changed from to Deafness, autosomal dominant 4A, MIM# 600652; Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369
Mendeliome v0.14277 MYH14 Zornitza Stark Publications for gene: MYH14 were set to
Mendeliome v0.14276 MYH14 Zornitza Stark Mode of inheritance for gene: MYH14 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14275 MYH14 Zornitza Stark reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: None; Publications: 15015131, 25719458, 31045651, 28221712, 34681017, 21480433, 31653586, 31631044, 31231018; Phenotypes: Deafness, autosomal dominant 4A, MIM# 600652, Peripheral neuropathy, myopathy, hoarseness, and hearing loss 614369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14275 MYH3 Zornitza Stark Gene: myh3 has been classified as Green List (High Evidence).
Mendeliome v0.14275 MYH3 Zornitza Stark Phenotypes for gene: MYH3 were changed from to Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436; Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469
Mendeliome v0.14274 MYH3 Zornitza Stark Publications for gene: MYH3 were set to
Mendeliome v0.14273 MYH3 Zornitza Stark Mode of inheritance for gene: MYH3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14272 MYH3 Zornitza Stark reviewed gene: MYH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25957469, 26544689, 21531865, 18695058; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon) 193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall) 618436, Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A 178110, Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B 618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14272 MYO1E Zornitza Stark Gene: myo1e has been classified as Green List (High Evidence).
Mendeliome v0.14272 MYO1E Zornitza Stark Phenotypes for gene: MYO1E were changed from to Glomerulosclerosis, focal segmental, 6, MIM# 614131
Mendeliome v0.14271 MYO1E Zornitza Stark Publications for gene: MYO1E were set to
Mendeliome v0.14270 MYO1E Zornitza Stark Mode of inheritance for gene: MYO1E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14269 MYO1E Zornitza Stark reviewed gene: MYO1E: Rating: GREEN; Mode of pathogenicity: None; Publications: 21756023, 31520189, 25739341, 23977349; Phenotypes: Glomerulosclerosis, focal segmental, 6, MIM# 614131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14269 WNT1 Zornitza Stark Marked gene: WNT1 as ready
Mendeliome v0.14269 WNT1 Zornitza Stark Gene: wnt1 has been classified as Green List (High Evidence).
Mendeliome v0.14269 WNT1 Zornitza Stark Phenotypes for gene: WNT1 were changed from to Osteogenesis imperfecta, type XV, MIM# 615220
Mendeliome v0.14268 WNT1 Zornitza Stark Publications for gene: WNT1 were set to
Mendeliome v0.14267 WNT1 Zornitza Stark Mode of inheritance for gene: WNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14266 WNT1 Zornitza Stark reviewed gene: WNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23499309, 23499310, 23656646, 26671912; Phenotypes: Osteogenesis imperfecta, type XV, MIM# 615220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14266 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
Mendeliome v0.14266 WNK4 Zornitza Stark Phenotypes for gene: WNK4 were changed from to Pseudohypoaldosteronism, type IIB, MIM# 614491
Mendeliome v0.14265 WNK4 Zornitza Stark Publications for gene: WNK4 were set to
Mendeliome v0.14264 WNK4 Zornitza Stark Mode of inheritance for gene: WNK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14263 WNK4 Zornitza Stark reviewed gene: WNK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22266938, 31044551; Phenotypes: Pseudohypoaldosteronism, type IIB, MIM# 614491; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14263 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
Mendeliome v0.14263 WNK1 Zornitza Stark Phenotypes for gene: WNK1 were changed from to Neuropathy, hereditary sensory and autonomic, type II, MIM# 201300; MONDO:0024309; Pseudohypoaldosteronism, type IIC, MIM# 614492
Mendeliome v0.14262 WNK1 Zornitza Stark Publications for gene: WNK1 were set to
Mendeliome v0.14261 WNK1 Zornitza Stark Mode of inheritance for gene: WNK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14260 WNK1 Zornitza Stark changed review comment from: Well established gene-disease association.

Note mono-allelic variants are associated with pseudohypoaldosteronism; to: Well established gene-disease associations.
Mendeliome v0.14260 WNK1 Zornitza Stark edited their review of gene: WNK1: Changed phenotypes: Neuropathy, hereditary sensory and autonomic, type II, MIM# 201300, MONDO:0024309, Pseudohypoaldosteronism, type IIC, MIM# 614492; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14260 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Mendeliome v0.14260 WDR4 Zornitza Stark Phenotypes for gene: WDR4 were changed from to Galloway-Mowat syndrome 6, OMIM #618347; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Mendeliome v0.14259 WDR4 Zornitza Stark Publications for gene: WDR4 were set to
Mendeliome v0.14258 WDR4 Zornitza Stark Mode of inheritance for gene: WDR4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14257 WDR4 Zornitza Stark reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26416026, 30079490, 29597095, 28617965; Phenotypes: Galloway-Mowat syndrome 6, OMIM #618347, Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14257 WDR36 Zornitza Stark Classified gene: WDR36 as Amber List (moderate evidence)
Mendeliome v0.14257 WDR36 Zornitza Stark Gene: wdr36 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14256 WDR36 Zornitza Stark changed review comment from: Multiple individuals reported.

However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000.; to: Multiple individuals reported. Adult-onset.

However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000.
Mendeliome v0.14256 WDR36 Zornitza Stark edited their review of gene: WDR36: Changed rating: AMBER
Mendeliome v0.14256 WDR36 Zornitza Stark edited their review of gene: WDR36: Changed publications: 15677485, 18172102, 20813748, 34681019, 29540704
Mendeliome v0.14256 WDR36 Zornitza Stark changed review comment from: Multiple individuals reported.

However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad.; to: Multiple individuals reported.

However, note one of the earliest reported variants p.Asp658Gly is present in >1,000 individuals in gnomad, and another, p.Ala449Thr is present in >2000.
Mendeliome v0.14256 WDR36 Zornitza Stark Gene: wdr36 has been classified as Green List (High Evidence).
Mendeliome v0.14256 WDR36 Zornitza Stark Phenotypes for gene: WDR36 were changed from to Glaucoma 1, open angle, G, MIM# 609887
Mendeliome v0.14255 WDR36 Zornitza Stark Publications for gene: WDR36 were set to
Mendeliome v0.14254 WDR36 Zornitza Stark Mode of inheritance for gene: WDR36 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14253 WDR36 Zornitza Stark reviewed gene: WDR36: Rating: GREEN; Mode of pathogenicity: None; Publications: 15677485, 18172102, 20813748; Phenotypes: Glaucoma 1, open angle, G, MIM# 609887; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14253 WASHC5 Zornitza Stark Gene: washc5 has been classified as Green List (High Evidence).
Mendeliome v0.14253 WASHC5 Zornitza Stark Phenotypes for gene: WASHC5 were changed from to Ritscher-Schinzel syndrome 1, MIM# 220210; Spastic paraplegia 8, autosomal dominant, MIM# 603563
Mendeliome v0.14252 WASHC5 Zornitza Stark Publications for gene: WASHC5 were set to
Mendeliome v0.14251 WASHC5 Zornitza Stark Mode of inheritance for gene: WASHC5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14250 WASHC5 Zornitza Stark reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160902, 23455931, 30778698, 24065355, 33456446; Phenotypes: Ritscher-Schinzel syndrome 1, MIM# 220210, Spastic paraplegia 8, autosomal dominant, MIM# 603563; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14250 WASF1 Zornitza Stark Gene: wasf1 has been classified as Green List (High Evidence).
Mendeliome v0.14250 WASF1 Zornitza Stark Phenotypes for gene: WASF1 were changed from to Neurodevelopmental disorder with absent language and variable seizures , MIM#618707
Mendeliome v0.14249 WASF1 Zornitza Stark Publications for gene: WASF1 were set to
Mendeliome v0.14248 WASF1 Zornitza Stark Mode of inheritance for gene: WASF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14247 WASF1 Zornitza Stark reviewed gene: WASF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961568, 34845217, 34478686, 34356165; Phenotypes: Neurodevelopmental disorder with absent language and variable seizures , MIM#618707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14247 WAC Zornitza Stark Gene: wac has been classified as Green List (High Evidence).
Mendeliome v0.14247 WAC Zornitza Stark Phenotypes for gene: WAC were changed from to Desanto-Shinawi syndrome, MIM# 616708
Mendeliome v0.14246 WAC Zornitza Stark Publications for gene: WAC were set to
Mendeliome v0.14245 WAC Zornitza Stark Mode of inheritance for gene: WAC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14244 WAC Zornitza Stark reviewed gene: WAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26264232, 25356899, 35266333; Phenotypes: Desanto-Shinawi syndrome, MIM# 616708; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14244 RNASEH1 Belinda Chong reviewed gene: RNASEH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26094573, 31258551; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 MIM#616479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14244 FXYD2 Bryony Thompson Gene: fxyd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14244 FXYD2 Bryony Thompson Phenotypes for gene: FXYD2 were changed from to Renal hypomagnesemia 2 MONDO:0007937
Mendeliome v0.14243 FXYD2 Bryony Thompson Publications for gene: FXYD2 were set to
Mendeliome v0.14242 FXYD2 Bryony Thompson Mode of pathogenicity for gene: FXYD2 was changed from to Other
Mendeliome v0.14241 FXYD2 Bryony Thompson Mode of inheritance for gene: FXYD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14240 FXYD2 Bryony Thompson Classified gene: FXYD2 as Amber List (moderate evidence)
Mendeliome v0.14240 FXYD2 Bryony Thompson Gene: fxyd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14239 FXYD2 Bryony Thompson reviewed gene: FXYD2: Rating: AMBER; Mode of pathogenicity: Other; Publications: 17980699, 12763862, 18448590, 11062458, 25765846, 27014088; Phenotypes: Renal hypomagnesemia 2 MONDO:0007937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14239 RIPPLY2 Zornitza Stark Gene: ripply2 has been classified as Green List (High Evidence).
Mendeliome v0.14239 RIPPLY2 Zornitza Stark Phenotypes for gene: RIPPLY2 were changed from to Spondylocostal dysostosis 6, MIM# 616566
Mendeliome v0.14238 RIPPLY2 Zornitza Stark Publications for gene: RIPPLY2 were set to
Mendeliome v0.14237 RIPPLY2 Zornitza Stark Mode of inheritance for gene: RIPPLY2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14236 RIPPLY2 Zornitza Stark edited their review of gene: RIPPLY2: Changed rating: GREEN
Mendeliome v0.14236 RIPPLY2 Zornitza Stark reviewed gene: RIPPLY2: Rating: ; Mode of pathogenicity: None; Publications: 25343988, 33410135, 32212228, 29761784; Phenotypes: Spondylocostal dysostosis 6, MIM# 616566; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14236 FXN Bryony Thompson Gene: fxn has been classified as Green List (High Evidence).
Mendeliome v0.14236 MYOC Zornitza Stark Gene: myoc has been classified as Green List (High Evidence).
Mendeliome v0.14236 MYOC Zornitza Stark Phenotypes for gene: MYOC were changed from to Glaucoma 1A, primary open angle, MIM# 137750
Mendeliome v0.14235 MYOC Zornitza Stark Publications for gene: MYOC were set to
Mendeliome v0.14234 MYOC Zornitza Stark Mode of inheritance for gene: MYOC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14233 MYOC Zornitza Stark reviewed gene: MYOC: Rating: GREEN; Mode of pathogenicity: None; Publications: 9005853, 9535666, 15108121; Phenotypes: Glaucoma 1A, primary open angle, MIM# 137750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14233 MYOCD Zornitza Stark Mode of inheritance for gene: MYOCD was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14232 MYOCD Zornitza Stark edited their review of gene: MYOCD: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14232 MYOCD Zornitza Stark changed review comment from: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females.

Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance.

Additional family in PMID 35005812 as part of a large prenatal renal cohort.; to: Congenital megabladder (MGBL) is characterized by a massively dilated bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, likely the result of differences in urethra and bladder development and length differences in urethra between males and females.

Seven affected males from three families. Five females and one male with the variant were unaffected, suggesting incomplete penetrance.

Additional family in PMID 35005812 as part of a large prenatal renal cohort.

Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease).

Mouse models.
Mendeliome v0.14232 MYOCD Zornitza Stark Gene: myocd has been classified as Green List (High Evidence).
Mendeliome v0.14232 MYOCD Zornitza Stark Phenotypes for gene: MYOCD were changed from to Megabladder, congenital, MIM# 618719
Mendeliome v0.14231 MYOCD Zornitza Stark Publications for gene: MYOCD were set to
Mendeliome v0.14230 MYOCD Zornitza Stark Mode of inheritance for gene: MYOCD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14229 MYOCD Zornitza Stark edited their review of gene: MYOCD: Changed phenotypes: Megabladder, congenital, MIM# 618719
Mendeliome v0.14229 MYOCD Zornitza Stark reviewed gene: MYOCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 31513549, 35005812; Phenotypes: Megabladder, congenital, MIM3 618719; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14229 MYOT Zornitza Stark Marked gene: MYOT as ready
Mendeliome v0.14229 MYOT Zornitza Stark Gene: myot has been classified as Green List (High Evidence).
Mendeliome v0.14229 MYOT Zornitza Stark Phenotypes for gene: MYOT were changed from to Myopathy, myofibrillar, 3, MIM# 609200; Myopathy, spheroid body, MIM# 182920
Mendeliome v0.14228 MYOT Zornitza Stark Publications for gene: MYOT were set to
Mendeliome v0.14227 MYOT Zornitza Stark Mode of inheritance for gene: MYOT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14226 MYOT Zornitza Stark reviewed gene: MYOT: Rating: GREEN; Mode of pathogenicity: None; Publications: 10958653, 15111675, 16380616, 33250842, 32509353, 29924655; Phenotypes: Myopathy, myofibrillar, 3, MIM# 609200, Myopathy, spheroid body, MIM# 182920; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14226 FXN Bryony Thompson Phenotypes for gene: FXN were changed from to Friedreich ataxia MONDO:0100339
Mendeliome v0.14225 FXN Bryony Thompson Publications for gene: FXN were set to
Mendeliome v0.14224 FXN Bryony Thompson Mode of inheritance for gene: FXN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14223 FXN Bryony Thompson edited their review of gene: FXN: Added comment: Well-established gene-disease association. 96% of cases are caused by biallelic intronic GAA triplet repeat expansion and 4% are attributable to biallelic single nucleotide variants and small indels. Loss of function is the mechanism of disease.; Changed rating: GREEN; Changed publications: 20301458, 26704351; Changed phenotypes: Friedreich ataxia MONDO:0100339; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Set current diagnostic: yes
Mendeliome v0.14223 RNF139 Belinda Chong reviewed gene: RNF139: Rating: RED; Mode of pathogenicity: None; Publications: 9689122; Phenotypes: Renal cell carcinoma MIM#144700; Mode of inheritance: Other
Mendeliome v0.14223 FUT8 Bryony Thompson Marked gene: FUT8 as ready
Mendeliome v0.14223 FUT8 Bryony Thompson Gene: fut8 has been classified as Green List (High Evidence).
Mendeliome v0.14223 FUT8 Bryony Thompson Phenotypes for gene: FUT8 were changed from to Congenital disorder of glycosylation with defective fucosylation 1 MONDO:0020775
Mendeliome v0.14222 FUT8 Bryony Thompson Publications for gene: FUT8 were set to
Mendeliome v0.14221 FUT8 Bryony Thompson Mode of inheritance for gene: FUT8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14220 FUT8 Bryony Thompson reviewed gene: FUT8: Rating: GREEN; Mode of pathogenicity: None; Publications: 29304374, 34389986, 32049367, 16236725; Phenotypes: Congenital disorder of glycosylation with defective fucosylation 1 MONDO:0020775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14220 FUT1 Bryony Thompson Marked gene: FUT1 as ready
Mendeliome v0.14220 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14220 FUT1 Bryony Thompson Phenotypes for gene: FUT1 were changed from to [Bombay phenotype] MIM#616754
Mendeliome v0.14219 FUT1 Bryony Thompson Classified gene: FUT1 as Red List (low evidence)
Mendeliome v0.14219 FUT1 Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants produce the Bombay blood group, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene.
Mendeliome v0.14219 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14218 FUT1 Bryony Thompson Deleted their comment
Mendeliome v0.14218 FUT1 Bryony Thompson Publications for gene: FUT1 were set to
Mendeliome v0.14217 FUT1 Bryony Thompson Classified gene: FUT1 as Red List (low evidence)
Mendeliome v0.14217 FUT1 Bryony Thompson Added comment: Comment on list classification: Biallelic loss of function variants cause Bombay phenotype, which is a recessive H-deficient red blood cell phenotype. Bombay and para-Bombay individuals display no apparent deleterious phenotype except in circumstances requiring blood transfusion. No evidence for Mendelian disease associated with this gene.
Mendeliome v0.14217 FUT1 Bryony Thompson Gene: fut1 has been classified as Red List (Low Evidence).
Mendeliome v0.14216 FUT1 Bryony Thompson Mode of inheritance for gene: FUT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14215 FSHR Bryony Thompson Gene: fshr has been classified as Green List (High Evidence).
Mendeliome v0.14215 FTO Bryony Thompson Marked gene: FTO as ready
Mendeliome v0.14215 FTO Bryony Thompson Gene: fto has been classified as Green List (High Evidence).
Mendeliome v0.14215 FTO Bryony Thompson Publications for gene: FTO were set to
Mendeliome v0.14214 FTO Bryony Thompson Phenotypes for gene: FTO were changed from to Growth retardation, developmental delay, facial dysmorphism MIM#612938
Mendeliome v0.14213 FTO Bryony Thompson Mode of inheritance for gene: FTO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14212 FTO Bryony Thompson reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234441, 19559399, 26378117, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism MIM#612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14212 RIMS1 Zornitza Stark Gene: rims1 has been classified as Green List (High Evidence).
Mendeliome v0.14212 RIMS1 Zornitza Stark Phenotypes for gene: RIMS1 were changed from to Cone-rod dystrophy 7 , MIM#603649; Autism MONDO:0005260
Mendeliome v0.14211 RIMS1 Zornitza Stark Publications for gene: RIMS1 were set to
Mendeliome v0.14210 RIMS1 Zornitza Stark Mode of inheritance for gene: RIMS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14209 RIMS1 Zornitza Stark reviewed gene: RIMS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12659814, 25284784, 25961944; Phenotypes: Cone-rod dystrophy 7 , MIM#603649, Autism MONDO:0005260; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14209 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Mendeliome v0.14209 FSHR Bryony Thompson Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972
Mendeliome v0.14208 RHEB Zornitza Stark Phenotypes for gene: RHEB were changed from to Neurodevelopmental disorder MONDO:0700092, RHEB-related; Intellectual disability; Macrocephaly; Focal cortical dysplasia
Mendeliome v0.14207 RHEB Zornitza Stark Publications for gene: RHEB were set to
Mendeliome v0.14206 RHEB Zornitza Stark Mode of inheritance for gene: RHEB was changed from Unknown to Other
Mendeliome v0.14205 RHEB Zornitza Stark reviewed gene: RHEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31337748, 29051493; Phenotypes: Neurodevelopmental disorder MONDO:0700092, RHEB-related, Intellectual disability, Macrocephaly, Focal cortical dysplasia; Mode of inheritance: Other
Mendeliome v0.14205 FSHR Bryony Thompson Publications for gene: FSHR were set to
Mendeliome v0.14204 FSHR Bryony Thompson Mode of inheritance for gene: FSHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14203 FSHR Bryony Thompson reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14203 RHCE Zornitza Stark Gene: rhce has been classified as Green List (High Evidence).
Mendeliome v0.14203 RHCE Zornitza Stark Phenotypes for gene: RHCE were changed from to Rh-null disease, amorph type, MIM# 617970
Mendeliome v0.14202 RHCE Zornitza Stark Publications for gene: RHCE were set to
Mendeliome v0.14201 RHCE Zornitza Stark Mode of inheritance for gene: RHCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14200 RHCE Zornitza Stark reviewed gene: RHCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 9657766, 16271106, 25413218; Phenotypes: Rh-null disease, amorph type, MIM# 617970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14200 RGS9BP Zornitza Stark Gene: rgs9bp has been classified as Green List (High Evidence).
Mendeliome v0.14200 RGS9BP Zornitza Stark Phenotypes for gene: RGS9BP were changed from to Bradyopsia, MIM# 608415
Mendeliome v0.14199 RGS9BP Zornitza Stark Publications for gene: RGS9BP were set to
Mendeliome v0.14198 RGS9BP Zornitza Stark Mode of inheritance for gene: RGS9BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14197 RGS9BP Zornitza Stark reviewed gene: RGS9BP: Rating: GREEN; Mode of pathogenicity: None; Publications: 14702087, 19818506; Phenotypes: Bradyopsia, MIM# 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14197 RGS9 Zornitza Stark Gene: rgs9 has been classified as Green List (High Evidence).
Mendeliome v0.14197 RGS9 Zornitza Stark Phenotypes for gene: RGS9 were changed from to Bradyopsia, MIM# 608415
Mendeliome v0.14196 RGS9 Zornitza Stark Publications for gene: RGS9 were set to
Mendeliome v0.14195 RGS9 Zornitza Stark Mode of inheritance for gene: RGS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14194 RGS9 Zornitza Stark reviewed gene: RGS9: Rating: GREEN; Mode of pathogenicity: None; Publications: 14702087, 10676965, 19818506; Phenotypes: Bradyopsia, MIM# 608415; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14194 RFX6 Zornitza Stark reviewed gene: RFX6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitchell-Riley syndrome, MIM# 615710; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14194 RFX6 Zornitza Stark Gene: rfx6 has been classified as Green List (High Evidence).
Mendeliome v0.14194 RFX6 Zornitza Stark Phenotypes for gene: RFX6 were changed from to Mitchell-Riley syndrome, MIM# 615710
Mendeliome v0.14193 RFX6 Zornitza Stark Publications for gene: RFX6 were set to
Mendeliome v0.14192 SEMA7A Zornitza Stark Phenotypes for gene: SEMA7A were changed from Decreased bone mineral density; Kallmann syndrome; progressive familial intrahepatic cholestasis to Decreased bone mineral density; Kallmann syndrome; Cholestasis, progressive familial intrahepatic, 11 , MIM# 619874
Mendeliome v0.14191 SEMA7A Zornitza Stark edited their review of gene: SEMA7A: Changed rating: AMBER; Changed phenotypes: Cholestasis, progressive familial intrahepatic, 11 , MIM# 619874; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14191 FXYD6 Bryony Thompson Gene: fxyd6 has been classified as Red List (Low Evidence).
Mendeliome v0.14191 FXYD6 Bryony Thompson Phenotypes for gene: FXYD6 were changed from to Schizophrenia MONDO:0005090
Mendeliome v0.14190 FXYD6 Bryony Thompson Publications for gene: FXYD6 were set to
Mendeliome v0.14189 FXYD6 Bryony Thompson Classified gene: FXYD6 as Red List (low evidence)
Mendeliome v0.14189 FXYD6 Bryony Thompson Gene: fxyd6 has been classified as Red List (Low Evidence).
Mendeliome v0.14188 FXYD6 Bryony Thompson reviewed gene: FXYD6: Rating: RED; Mode of pathogenicity: None; Publications: 17357072, 26193471, 29895895; Phenotypes: Schizophrenia MONDO:0005090; Mode of inheritance: None
Mendeliome v0.14188 FZD2 Bryony Thompson Gene: fzd2 has been classified as Green List (High Evidence).
Mendeliome v0.14188 FZD2 Bryony Thompson Phenotypes for gene: FZD2 were changed from to Autosomal dominant omodysplasia MONDO:0008123
Mendeliome v0.14187 FZD2 Bryony Thompson Publications for gene: FZD2 were set to
Mendeliome v0.14186 FBP2 Zornitza Stark Gene: fbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14186 FBP2 Zornitza Stark Classified gene: FBP2 as Amber List (moderate evidence)
Mendeliome v0.14186 FBP2 Zornitza Stark Gene: fbp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14185 FBP2 Zornitza Stark gene: FBP2 was added
gene: FBP2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBP2 were set to 33977262
Phenotypes for gene: FBP2 were set to Leukodystrophy, childhood-onset, remitting, MIM# 619864
Review for gene: FBP2 was set to AMBER
Added comment: 8 individuals from 3 generations in a single family reported with a variant in this gene. The children presented with episode of regression and leukodystrophy in early childhood, from which they made a slow recovery. The adults had a broad range of neurobehavioural phenotypes but also had leukodystrophy on imaging. Some functional data presented (in vitro).
Sources: Expert list
Mendeliome v0.14184 TLR7 Zornitza Stark Phenotypes for gene: TLR7 were changed from Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051 to Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051; Systemic lupus erythematosus 17, MIM# 301080
Mendeliome v0.14183 TLR7 Zornitza Stark Publications for gene: TLR7 were set to 32706371
Mendeliome v0.14182 TLR7 Zornitza Stark Mode of inheritance for gene: TLR7 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14181 TLR7 Zornitza Stark changed review comment from: Four affected individuals from two unrelated families and some functional data.; to: Immunodeficiency: Four affected individuals from two unrelated families and some functional data.
Mendeliome v0.14181 TLR7 Zornitza Stark edited their review of gene: TLR7: Added comment: SLE
XLD: only affected females reported; 4 individuals from three unrelated families. Mouse model.; Changed publications: 32706371, 35477763; Changed phenotypes: Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051, Systemic lupus erythematosus 17, MIM# 301080; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14181 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14181 MOV10L1 Zornitza Stark Classified gene: MOV10L1 as Amber List (moderate evidence)
Mendeliome v0.14181 MOV10L1 Zornitza Stark Gene: mov10l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14180 MOV10L1 Zornitza Stark gene: MOV10L1 was added
gene: MOV10L1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MOV10L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOV10L1 were set to 35476666; 20534472
Phenotypes for gene: MOV10L1 were set to Spermatogenic failure 73, MIM#619878
Review for gene: MOV10L1 was set to AMBER
Added comment: Two unrelated individuals and a mouse model.
Sources: Expert list
Mendeliome v0.14179 RFX6 Zornitza Stark Mode of inheritance for gene: RFX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14178 RFC2 Zornitza Stark Classified gene: RFC2 as Red List (low evidence)
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14177 RFC2 Zornitza Stark reviewed gene: RFC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14177 REST Zornitza Stark Marked gene: REST as ready
Mendeliome v0.14177 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Mendeliome v0.14177 REST Zornitza Stark Phenotypes for gene: REST were changed from to Deafness, autosomal dominant 27, MIM# 612431; {Wilms tumor 6, susceptibility to}, MIM# 616806; Fibromatosis, gingival, 5, MIM# 617626
Mendeliome v0.14176 REST Zornitza Stark Publications for gene: REST were set to
Mendeliome v0.14175 REST Zornitza Stark Mode of inheritance for gene: REST was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14174 REST Zornitza Stark reviewed gene: REST: Rating: GREEN; Mode of pathogenicity: None; Publications: 29961578, 34828371, 26551668, 28686854; Phenotypes: Deafness, autosomal dominant 27, MIM# 612431, {Wilms tumor 6, susceptibility to}, MIM# 616806, Fibromatosis, gingival, 5, MIM# 617626; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14174 REEP6 Zornitza Stark Gene: reep6 has been classified as Green List (High Evidence).
Mendeliome v0.14174 REEP6 Zornitza Stark Phenotypes for gene: REEP6 were changed from to Retinitis pigmentosa 77, MIM# 617304
Mendeliome v0.14173 REEP6 Zornitza Stark Publications for gene: REEP6 were set to
Mendeliome v0.14172 RP1 Belinda Chong reviewed gene: RP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391211, 10465120, 10465120, 10484783, 29425069, 31213501; Phenotypes: Retinitis pigmentosa 1 MIM#180100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14172 REEP6 Zornitza Stark Mode of inheritance for gene: REEP6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14171 REEP6 Zornitza Stark reviewed gene: REEP6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27889058, 33917198, 31538292, 29120066, 28475715; Phenotypes: Retinitis pigmentosa 77, MIM# 617304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14171 RCBTB1 Zornitza Stark Marked gene: RCBTB1 as ready
Mendeliome v0.14171 RCBTB1 Zornitza Stark Gene: rcbtb1 has been classified as Green List (High Evidence).
Mendeliome v0.14171 RCBTB1 Zornitza Stark Phenotypes for gene: RCBTB1 were changed from to Retinal dystrophy with or without extraocular anomalies, MIM# 617175
Mendeliome v0.14170 RCBTB1 Zornitza Stark Publications for gene: RCBTB1 were set to
Mendeliome v0.14169 RCBTB1 Zornitza Stark Mode of inheritance for gene: RCBTB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14168 RCBTB1 Zornitza Stark reviewed gene: RCBTB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486781, 35057699, 33624564, 33104391; Phenotypes: Retinal dystrophy with or without extraocular anomalies, MIM# 617175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14168 FZD2 Bryony Thompson Mode of inheritance for gene: FZD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14167 FZD2 Bryony Thompson reviewed gene: FZD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25759469, 30455931, 29383834, 29230162; Phenotypes: Autosomal dominant omodysplasia MONDO:0008123; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14167 FSHB Bryony Thompson Gene: fshb has been classified as Green List (High Evidence).
Mendeliome v0.14167 FSHB Bryony Thompson Phenotypes for gene: FSHB were changed from to Hypogonadotropic hypogonadism 24 without anosmia MONDO:0009239
Mendeliome v0.14166 FSHB Bryony Thompson Publications for gene: FSHB were set to
Mendeliome v0.14165 FSHB Bryony Thompson Mode of inheritance for gene: FSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14164 FSHB Bryony Thompson reviewed gene: FSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 8220432, 9280841, 9624193, 9806482, 9271483, 16630814; Phenotypes: Hypogonadotropic hypogonadism 24 without anosmia MONDO:0009239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14164 FRZB Bryony Thompson Gene: frzb has been classified as Red List (Low Evidence).
Mendeliome v0.14164 FRZB Bryony Thompson Phenotypes for gene: FRZB were changed from to {Osteoarthritis susceptibility 1} MIM#165720
Mendeliome v0.14163 FRRS1L Bryony Thompson Gene: frrs1l has been classified as Green List (High Evidence).
Mendeliome v0.14163 FRRS1L Bryony Thompson Phenotypes for gene: FRRS1L were changed from to Developmental and epileptic encephalopathy, 37 MONDO:0014859
Mendeliome v0.14162 FRZB Bryony Thompson Publications for gene: FRZB were set to
Mendeliome v0.14161 FRZB Bryony Thompson Classified gene: FRZB as Red List (low evidence)
Mendeliome v0.14161 FRZB Bryony Thompson Gene: frzb has been classified as Red List (Low Evidence).
Mendeliome v0.14160 FRRS1L Bryony Thompson Publications for gene: FRRS1L were set to
Mendeliome v0.14159 FRRS1L Bryony Thompson Mode of inheritance for gene: FRRS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14158 FRZB Bryony Thompson reviewed gene: FRZB: Rating: RED; Mode of pathogenicity: None; Publications: 15210948; Phenotypes: {Osteoarthritis susceptibility 1} MIM#165720; Mode of inheritance: Unknown
Mendeliome v0.14158 FRRS1L Bryony Thompson reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27236917, 27239025, 30692144; Phenotypes: Developmental and epileptic encephalopathy, 37 MONDO:0014859; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14158 FOXN1 Bryony Thompson Gene: foxn1 has been classified as Green List (High Evidence).
Mendeliome v0.14158 RBPJ Zornitza Stark Gene: rbpj has been classified as Green List (High Evidence).
Mendeliome v0.14158 RBPJ Zornitza Stark Phenotypes for gene: RBPJ were changed from to Adams-Oliver syndrome 3, MIM# 614814
Mendeliome v0.14157 FOXN1 Bryony Thompson Phenotypes for gene: FOXN1 were changed from to T-cell immunodeficiency, congenital alopecia, and nail dystrophy MONDO:0011132
Mendeliome v0.14156 RBPJ Zornitza Stark Publications for gene: RBPJ were set to
Mendeliome v0.14155 RBPJ Zornitza Stark Mode of inheritance for gene: RBPJ was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14154 RBPJ Zornitza Stark reviewed gene: RBPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 22883147, 29924900; Phenotypes: Adams-Oliver syndrome 3, MIM# 614814; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14154 FOXN1 Bryony Thompson Publications for gene: FOXN1 were set to
Mendeliome v0.14153 FOXN1 Bryony Thompson Mode of inheritance for gene: FOXN1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14152 FOXN1 Bryony Thompson reviewed gene: FOXN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10206641, 20978268, 20978268, 28636882, 31566583, 31447097; Phenotypes: T-cell immunodeficiency, congenital alopecia, and nail dystrophy MONDO:0011132; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14152 FOXI1 Bryony Thompson Gene: foxi1 has been classified as Green List (High Evidence).
Mendeliome v0.14152 FOXI1 Bryony Thompson Phenotypes for gene: FOXI1 were changed from to autosomal recessive distal renal tubular acidosis MONDO:0018440
Mendeliome v0.14151 FOXI1 Bryony Thompson Publications for gene: FOXI1 were set to
Mendeliome v0.14150 FOXI1 Bryony Thompson Mode of inheritance for gene: FOXI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14149 FOXI1 Bryony Thompson reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843211, 12642503, 29242249, 17503324, 30268946, 27997596, 22285650, 23965030, 24860705, 32447495, 19204907; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14149 FOXD3 Bryony Thompson Gene: foxd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14149 FOXD3 Bryony Thompson Phenotypes for gene: FOXD3 were changed from to Autoimmune disease, susceptibility to, 1 MONDO:0011919
Mendeliome v0.14148 FOXD3 Bryony Thompson Publications for gene: FOXD3 were set to
Mendeliome v0.14147 FOXD3 Bryony Thompson Classified gene: FOXD3 as Red List (low evidence)
Mendeliome v0.14147 FOXD3 Bryony Thompson Gene: foxd3 has been classified as Red List (Low Evidence).
Mendeliome v0.14146 FOXD3 Bryony Thompson reviewed gene: FOXD3: Rating: RED; Mode of pathogenicity: None; Publications: 16098053; Phenotypes: Autoimmune disease, susceptibility to, 1 MONDO:0011919; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14146 FMR1 Bryony Thompson Gene: fmr1 has been classified as Green List (High Evidence).
Mendeliome v0.14146 FMR1 Bryony Thompson Phenotypes for gene: FMR1 were changed from to Fragile X syndrome MONDO:0010383
Mendeliome v0.14145 RBP3 Zornitza Stark Gene: rbp3 has been classified as Green List (High Evidence).
Mendeliome v0.14145 RBP3 Zornitza Stark Phenotypes for gene: RBP3 were changed from to Retinitis pigmentosa 66, MIM# 615233
Mendeliome v0.14144 RBP3 Zornitza Stark Publications for gene: RBP3 were set to
Mendeliome v0.14143 RBP3 Zornitza Stark Mode of inheritance for gene: RBP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14142 RBP3 Zornitza Stark reviewed gene: RBP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19074801, 29571629, 26066594, 25766589; Phenotypes: Retinitis pigmentosa 66, MIM# 615233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14142 RBM28 Zornitza Stark Gene: rbm28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14142 RBM28 Zornitza Stark Phenotypes for gene: RBM28 were changed from to Alopecia, neurologic defects, and endocrinopathy syndrome (MIM#612079)
Mendeliome v0.14141 RBM28 Zornitza Stark Publications for gene: RBM28 were set to
Mendeliome v0.14140 RBM28 Zornitza Stark Mode of inheritance for gene: RBM28 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14139 RBM28 Zornitza Stark Classified gene: RBM28 as Amber List (moderate evidence)
Mendeliome v0.14139 RBM28 Zornitza Stark Gene: rbm28 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14138 RASGRP2 Zornitza Stark Gene: rasgrp2 has been classified as Green List (High Evidence).
Mendeliome v0.14138 RASGRP2 Zornitza Stark Phenotypes for gene: RASGRP2 were changed from to Bleeding disorder, platelet-type, 18 (MIM#615888)
Mendeliome v0.14137 RASGRP2 Zornitza Stark Publications for gene: RASGRP2 were set to
Mendeliome v0.14136 RASGRP2 Zornitza Stark Mode of inheritance for gene: RASGRP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14135 RBM28 Crystle Lee reviewed gene: RBM28: Rating: AMBER; Mode of pathogenicity: None; Publications: 18439547, 33941690, 27077951; Phenotypes: Alopecia, neurologic defects, and endocrinopathy syndrome (MIM#612079); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14135 RASGRP2 Crystle Lee reviewed gene: RASGRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28762304, 27663674, 28637664, 27235135; Phenotypes: Bleeding disorder, platelet-type, 18 (MIM#615888); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14135 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Mendeliome v0.14135 SCN2A Zornitza Stark Publications for gene: SCN2A were set to
Mendeliome v0.14134 SCN2A Zornitza Stark changed review comment from: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia.; to: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia. Rather than being discrete disorders, these probably represent a continuum of manifestations of a single brain channelopathy disorder.

Multiple families reported.
Mendeliome v0.14134 SCN2A Zornitza Stark edited their review of gene: SCN2A: Changed publications: 19786696, 23662938, 15028761, 30185235, 20956790, 24650168, 23935176, 22495306
Mendeliome v0.14134 SCN2A Zornitza Stark Phenotypes for gene: SCN2A were changed from to Episodic ataxia, type 9, MIM# 618924; Seizures, benign familial infantile, 3, MIM# 607745; Developmental and epileptic encephalopathy 11, MIM# 613721
Mendeliome v0.14133 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14132 SCN2A Zornitza Stark edited their review of gene: SCN2A: Changed phenotypes: Episodic ataxia, type 9, MIM# 618924, Seizures, benign familial infantile, 3, MIM# 607745, Developmental and epileptic encephalopathy 11, MIM# 613721
Mendeliome v0.14132 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14131 SCN9A Zornitza Stark Gene: scn9a has been classified as Green List (High Evidence).
Mendeliome v0.14131 SCN9A Zornitza Stark Phenotypes for gene: SCN9A were changed from to Erythermalgia, primary, MIM# 133020; Insensitivity to pain, congenital, MIM# 243000; Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000; Paroxysmal extreme pain disorder, MIM# 167400; Small fiber neuropathy,MIM# 133020
Mendeliome v0.14130 SCN9A Zornitza Stark Mode of inheritance for gene: SCN9A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14129 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Green List (High Evidence).
Mendeliome v0.14129 SLC22A5 Zornitza Stark Phenotypes for gene: SLC22A5 were changed from to Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919
Mendeliome v0.14128 SLC22A5 Zornitza Stark Publications for gene: SLC22A5 were set to
Mendeliome v0.14127 SLC22A5 Zornitza Stark Mode of inheritance for gene: SLC22A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14126 SLC22A12 Zornitza Stark Gene: slc22a12 has been classified as Green List (High Evidence).
Mendeliome v0.14126 SLC22A12 Zornitza Stark Phenotypes for gene: SLC22A12 were changed from to Hypouricemia, renal, MIM# 220150, MONDO:0020728
Mendeliome v0.14125 SLC22A12 Zornitza Stark Publications for gene: SLC22A12 were set to
Mendeliome v0.14124 SLC22A12 Zornitza Stark Mode of inheritance for gene: SLC22A12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14123 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Mendeliome v0.14123 SLC1A2 Zornitza Stark Phenotypes for gene: SLC1A2 were changed from to Developmental and epileptic encephalopathy 41, MIM# 617105
Mendeliome v0.14122 SLC1A2 Zornitza Stark Publications for gene: SLC1A2 were set to
Mendeliome v0.14121 SLC1A2 Zornitza Stark Mode of pathogenicity for gene: SLC1A2 was changed from to Other
Mendeliome v0.14120 SLC1A2 Zornitza Stark Mode of inheritance for gene: SLC1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14119 SLC1A2 Zornitza Stark reviewed gene: SLC1A2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27476654, 28777935, 30937933, 23934111; Phenotypes: Developmental and epileptic encephalopathy 41, MIM# 617105; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14119 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14119 SLC1A1 Zornitza Stark Phenotypes for gene: SLC1A1 were changed from to Dicarboxylic aminoaciduria, MIM# 222730
Mendeliome v0.14118 SLC1A1 Zornitza Stark Publications for gene: SLC1A1 were set to
Mendeliome v0.14117 SLC1A1 Zornitza Stark Mode of inheritance for gene: SLC1A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14116 SLC1A1 Zornitza Stark Classified gene: SLC1A1 as Amber List (moderate evidence)
Mendeliome v0.14116 SLC1A1 Zornitza Stark Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14115 SLC1A1 Zornitza Stark reviewed gene: SLC1A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21123949; Phenotypes: Dicarboxylic aminoaciduria, MIM# 222730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14115 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Mendeliome v0.14115 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Mendeliome v0.14114 SLC19A3 Zornitza Stark Publications for gene: SLC19A3 were set to
Mendeliome v0.14113 SLC19A3 Zornitza Stark Mode of inheritance for gene: SLC19A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14112 SLC19A3 Zornitza Stark reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 15871139, 20065143, 23482991, 24878502, 23589815, 24166474, 26975589, 27896110; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14112 SLC17A8 Zornitza Stark Gene: slc17a8 has been classified as Green List (High Evidence).
Mendeliome v0.14112 SLC17A8 Zornitza Stark Phenotypes for gene: SLC17A8 were changed from to Deafness, autosomal dominant 25, MIM# 605583
Mendeliome v0.14111 SLC17A8 Zornitza Stark Publications for gene: SLC17A8 were set to
Mendeliome v0.14110 SLC17A8 Zornitza Stark Mode of inheritance for gene: SLC17A8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14109 SLC17A8 Zornitza Stark reviewed gene: SLC17A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674745, 26797701, 28647561; Phenotypes: Deafness, autosomal dominant 25, MIM# 605583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14109 SLC17A3 Zornitza Stark Gene: slc17a3 has been classified as Red List (Low Evidence).
Mendeliome v0.14109 SLC17A3 Zornitza Stark Phenotypes for gene: SLC17A3 were changed from to [Uric acid concentration, serum, QTL4], MIM# 612671, {Gout susceptibility 4}, MIM#612671
Mendeliome v0.14108 SLC17A3 Zornitza Stark Publications for gene: SLC17A3 were set to
Mendeliome v0.14107 SLC17A3 Zornitza Stark Mode of inheritance for gene: SLC17A3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14106 SLC17A3 Zornitza Stark Classified gene: SLC17A3 as Red List (low evidence)
Mendeliome v0.14106 SLC17A3 Zornitza Stark Gene: slc17a3 has been classified as Red List (Low Evidence).
Mendeliome v0.14105 SLC16A1 Zornitza Stark Gene: slc16a1 has been classified as Green List (High Evidence).
Mendeliome v0.14105 SLC16A1 Zornitza Stark Phenotypes for gene: SLC16A1 were changed from to Erythrocyte lactate transporter defect, MIM# 245340; Hyperinsulinemic hypoglycaemia, familial, 7, MIM# 610021; Monocarboxylate transporter 1 deficiency, MIM# 616095
Mendeliome v0.14104 SLC16A1 Zornitza Stark Publications for gene: SLC16A1 were set to
Mendeliome v0.14103 SLC16A1 Zornitza Stark Mode of inheritance for gene: SLC16A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14102 SLC16A1 Zornitza Stark reviewed gene: SLC16A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25390740, 32170320; Phenotypes: Erythrocyte lactate transporter defect, MIM# 245340, Hyperinsulinemic hypoglycaemia, familial, 7, MIM# 610021, Monocarboxylate transporter 1 deficiency, MIM# 616095; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14102 SLC11A2 Zornitza Stark Gene: slc11a2 has been classified as Green List (High Evidence).
Mendeliome v0.14102 SLC11A2 Zornitza Stark Phenotypes for gene: SLC11A2 were changed from to Anaemia, hypochromic microcytic, with iron overload 1 MIM#206100
Mendeliome v0.14101 SLC11A2 Zornitza Stark Publications for gene: SLC11A2 were set to
Mendeliome v0.14100 SLC11A2 Zornitza Stark Mode of inheritance for gene: SLC11A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14099 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Mendeliome v0.14099 SH2D1A Zornitza Stark Phenotypes for gene: SH2D1A were changed from to Lymphoproliferative syndrome, X-linked, 1, MIM# 308240
Mendeliome v0.14098 SH2D1A Zornitza Stark Publications for gene: SH2D1A were set to
Mendeliome v0.14097 SH2D1A Zornitza Stark Mode of inheritance for gene: SH2D1A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14096 SH2D1A Zornitza Stark reviewed gene: SH2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphoproliferative syndrome, X-linked, 1, MIM# 308240; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14096 SGCG Zornitza Stark Gene: sgcg has been classified as Green List (High Evidence).
Mendeliome v0.14096 SGCG Zornitza Stark Phenotypes for gene: SGCG were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Mendeliome v0.14095 SGCG Zornitza Stark Publications for gene: SGCG were set to
Mendeliome v0.14094 SGCG Zornitza Stark Mode of inheritance for gene: SGCG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14093 FMR1 Bryony Thompson Publications for gene: FMR1 were set to
Mendeliome v0.14092 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Mendeliome v0.14092 FLVCR1 Bryony Thompson Phenotypes for gene: FLVCR1 were changed from to posterior column ataxia-retinitis pigmentosa syndrome MONDO:0012177
Mendeliome v0.14091 FLNC Bryony Thompson Gene: flnc has been classified as Green List (High Evidence).
Mendeliome v0.14091 FMR1 Bryony Thompson Mode of inheritance for gene: FMR1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14090 FMR1 Bryony Thompson reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8156595, 28176767, 29178241; Phenotypes: Fragile X syndrome MONDO:0010383; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14090 FLVCR1 Bryony Thompson Publications for gene: FLVCR1 were set to
Mendeliome v0.14089 FLVCR1 Bryony Thompson Mode of inheritance for gene: FLVCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14088 FLNC Bryony Thompson Phenotypes for gene: FLNC were changed from to Myofibrillar myopathy MONDO:0018943; Dilated cardiomyopathy MONDO:0005021; distal myopathy with posterior leg and anterior hand involvement MONDO:0013550
Mendeliome v0.14087 FLVCR1 Bryony Thompson edited their review of gene: FLVCR1: Added comment: At least 5 unrelated families reported with visual impairment and ataxia. Onset is usually in childhood.; Changed publications: 21070897, 22279524, 21267618; Changed phenotypes: posterior column ataxia-retinitis pigmentosa syndrome MONDO:0012177; Set current diagnostic: yes
Mendeliome v0.14087 FLVCR1 Bryony Thompson Deleted their comment
Mendeliome v0.14087 FLNC Bryony Thompson Publications for gene: FLNC were set to
Mendeliome v0.14086 FLNC Bryony Thompson Mode of inheritance for gene: FLNC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14085 FLNC Bryony Thompson reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 15929027, 32112656; Phenotypes: Myofibrillar myopathy MONDO:0018943, Dilated cardiomyopathy MONDO:0005021, distal myopathy with posterior leg and anterior hand involvement MONDO:0013550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.14085 FLNB Bryony Thompson edited their review of gene: FLNB: Changed phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, filamin-related bone disorder MONDO:0019690
Mendeliome v0.14085 FLNB Bryony Thompson edited their review of gene: FLNB: Changed phenotypes: filamin-related bone disorder MONDO:0019690
Mendeliome v0.14085 FLNB Bryony Thompson Phenotypes for gene: FLNB were changed from spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516 to spondylocarpotarsal synostosis syndrome MONDO:0010094; filamin-related bone disorder MONDO:0019690
Mendeliome v0.14084 FLNB Bryony Thompson Gene: flnb has been classified as Green List (High Evidence).
Mendeliome v0.14084 FLNB Bryony Thompson Phenotypes for gene: FLNB were changed from to spondylocarpotarsal synostosis syndrome MONDO:0010094; osteochondrodysplasia MONDO:0005516
Mendeliome v0.14083 FLNB Bryony Thompson Publications for gene: FLNB were set to
Mendeliome v0.14082 FLNB Bryony Thompson Mode of inheritance for gene: FLNB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14081 FLNB Bryony Thompson reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: None; Publications: 14991055, 17360453, 20301736, 29566257, 16801345, 22190451; Phenotypes: spondylocarpotarsal synostosis syndrome MONDO:0010094, osteochondrodysplasia MONDO:0005516; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14081 FLI1 Bryony Thompson Gene: fli1 has been classified as Green List (High Evidence).
Mendeliome v0.14081 FLI1 Bryony Thompson Phenotypes for gene: FLI1 were changed from to Bleeding disorder, platelet-type, 21 MONDO:0054577
Mendeliome v0.14080 FLI1 Bryony Thompson Publications for gene: FLI1 were set to
Mendeliome v0.14079 FLI1 Bryony Thompson Mode of inheritance for gene: FLI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14078 FLI1 Bryony Thompson reviewed gene: FLI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10891501, 10981960, 24100448, 28255014, 26316623; Phenotypes: Bleeding disorder, platelet-type, 21 MONDO:0054577; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14078 FKTN Bryony Thompson Tag deep intronic tag was added to gene: FKTN.
Mendeliome v0.14078 FLG Bryony Thompson Gene: flg has been classified as Green List (High Evidence).
Mendeliome v0.14078 ASS1 Elena Savva Gene: ass1 has been classified as Green List (High Evidence).
Mendeliome v0.14078 FLG Bryony Thompson Phenotypes for gene: FLG were changed from to Ichthyosis vulgaris MONDO:0024304
Mendeliome v0.14077 FLG Bryony Thompson Publications for gene: FLG were set to
Mendeliome v0.14076 FLG Bryony Thompson Mode of inheritance for gene: FLG was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14075 ASS1 Elena Savva Phenotypes for gene: ASS1 were changed from to Citrullinemia MIM#215700; Urea cycle disorders and inherited hyperammonaemias; disorder of amino acid metabolism
Mendeliome v0.14074 ASTN1 Elena Savva Marked gene: ASTN1 as ready
Mendeliome v0.14074 ASTN1 Elena Savva Gene: astn1 has been classified as Green List (High Evidence).
Mendeliome v0.14074 ASS1 Elena Savva Publications for gene: ASS1 were set to
Mendeliome v0.14074 ASS1 Elena Savva Mode of inheritance for gene: ASS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14073 ASTN1 Elena Savva Phenotypes for gene: ASTN1 were changed from to Polymicrogyria; hypoplastic corpus callosum
Mendeliome v0.14072 FLG Bryony Thompson reviewed gene: FLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 16444271, 19349982, 34608691; Phenotypes: Ichthyosis vulgaris MONDO:0024304; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14072 ASTN1 Elena Savva Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Mendeliome v0.14072 ASTN1 Elena Savva Publications for gene: ASTN1 were set to
Mendeliome v0.14072 ASTN1 Elena Savva Mode of inheritance for gene: ASTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14071 ASB10 Elena Savva Phenotypes for gene: ASB10 were changed from Glaucoma 1, open angle, F MIM#603383 to Glaucoma 1, open angle, F MIM#603383
Mendeliome v0.14070 FKTN Bryony Thompson Marked gene: FKTN as ready
Mendeliome v0.14070 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Mendeliome v0.14070 FKTN Bryony Thompson Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Mendeliome v0.14069 FKTN Bryony Thompson Publications for gene: FKTN were set to
Mendeliome v0.14068 FKTN Bryony Thompson Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14067 FKTN Bryony Thompson reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 9690476, 19017726, 20301385, 28680109; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14067 GSN Zornitza Stark Gene: gsn has been classified as Green List (High Evidence).
Mendeliome v0.14067 GSN Zornitza Stark Phenotypes for gene: GSN were changed from to Amyloidosis, Finnish type, MIM# 105120
Mendeliome v0.14066 GSN Zornitza Stark Publications for gene: GSN were set to
Mendeliome v0.14065 GSN Zornitza Stark Mode of inheritance for gene: GSN was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14064 GSN Zornitza Stark changed review comment from: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported.

Multiple families with same founder variant.; to: The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including lattice corneal dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported.

Multiple families with same founder variant, p.Asp187Asn, though other variants also reported.
Mendeliome v0.14064 GSN Zornitza Stark edited their review of gene: GSN: Changed publications: 2176164, 28139293
Mendeliome v0.14064 GSN Zornitza Stark reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 2176164; Phenotypes: Amyloidosis, Finnish type, MIM# 105120; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14064 GSS Zornitza Stark Gene: gss has been classified as Green List (High Evidence).
Mendeliome v0.14064 GSS Zornitza Stark Phenotypes for gene: GSS were changed from to Glutathione synthetase deficiency MIM#266130; Hemolytic anemia due to glutathione synthetase deficiency MIM#231900; Disorders of the gamma-glutamyl cycle
Mendeliome v0.14063 GSS Zornitza Stark Publications for gene: GSS were set to
Mendeliome v0.14062 GSS Zornitza Stark Mode of inheritance for gene: GSS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14061 GSS Zornitza Stark reviewed gene: GSS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9215686; Phenotypes: Glutathione synthetase deficiency, MIM# 266130, Haemolytic anemia due to glutathione synthetase deficiency 231900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14061 GTF3C3 Zornitza Stark Marked gene: GTF3C3 as ready
Mendeliome v0.14061 GTF3C3 Zornitza Stark Gene: gtf3c3 has been classified as Green List (High Evidence).
Mendeliome v0.14061 GTF3C3 Zornitza Stark Phenotypes for gene: GTF3C3 were changed from to Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Mendeliome v0.14060 GTF3C3 Zornitza Stark Publications for gene: GTF3C3 were set to
Mendeliome v0.14059 GTF3C3 Zornitza Stark Mode of inheritance for gene: GTF3C3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14058 GTF3C3 Zornitza Stark reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 28097321, 30552426; Phenotypes: Neurodevelopmental disorder MONDO:0700092, GTF3C3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14058 GUCA1A Zornitza Stark Gene: guca1a has been classified as Green List (High Evidence).
Mendeliome v0.14058 GUCA1A Zornitza Stark Phenotypes for gene: GUCA1A were changed from to Cone dystrophy-3, MIM# 602093; Cone-rod dystrophy 14, MIM# 602093
Mendeliome v0.14057 GUCA1A Zornitza Stark Publications for gene: GUCA1A were set to
Mendeliome v0.14056 GUCA1A Zornitza Stark Mode of inheritance for gene: GUCA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14055 GUCA1A Zornitza Stark reviewed gene: GUCA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 9425234, 15953638, 11146732, 28125083; Phenotypes: Cone dystrophy-3, MIM# 602093, Cone-rod dystrophy 14, MIM# 602093; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14055 ASB10 Elena Savva Publications for gene: ASB10 were set to PMID: 26713451; 22156576
Mendeliome v0.14055 ASB10 Elena Savva Mode of inheritance for gene: ASB10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14054 ASB10 Elena Savva Publications for gene: ASB10 were set to
Mendeliome v0.14054 ASB10 Elena Savva Mode of inheritance for gene: ASB10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14055 ASB10 Elena Savva Phenotypes for gene: ASB10 were changed from to Glaucoma 1, open angle, F MIM#603383
Mendeliome v0.14054 ASB10 Elena Savva Gene: asb10 has been classified as Red List (Low Evidence).
Mendeliome v0.14054 ASB10 Elena Savva Classified gene: ASB10 as Red List (low evidence)
Mendeliome v0.14054 ASB10 Elena Savva Gene: asb10 has been classified as Red List (Low Evidence).
Mendeliome v0.14053 ASB10 Elena Savva reviewed gene: ASB10: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26713451, 22156576; Phenotypes: Glaucoma 1, open angle, F MIM#603383; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14053 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Mendeliome v0.14053 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from to Muscular dystrophy-dystroglycanopathy MONDO:0018276
Mendeliome v0.14052 FKRP Bryony Thompson Publications for gene: FKRP were set to
Mendeliome v0.14051 FKRP Bryony Thompson Mode of inheritance for gene: FKRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14050 ART4 Elena Savva Phenotypes for gene: ART4 were changed from {Macular degeneration, age-related, 8} MIM#613778 to {Macular degeneration, age-related, 8} MIM#613778
Mendeliome v0.14050 ART4 Elena Savva Mode of inheritance for gene: ART4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14049 FKRP Bryony Thompson reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 11592034, 11741828, 14647208, 19299310, 19155270; Phenotypes: Muscular dystrophy-dystroglycanopathy MONDO:0018276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14049 ART4 Elena Savva Phenotypes for gene: ART4 were changed from to {Macular degeneration, age-related, 8} MIM#613778
Mendeliome v0.14048 ART4 Elena Savva Mode of inheritance for gene: ART4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14048 ART4 Elena Savva Marked gene: ART4 as ready
Mendeliome v0.14048 ART4 Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14048 ART4 Elena Savva Publications for gene: ART4 were set to
Mendeliome v0.14048 ART4 Elena Savva Classified gene: ART4 as Amber List (moderate evidence)
Mendeliome v0.14048 ART4 Elena Savva Gene: art4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14047 ART4 Elena Savva reviewed gene: ART4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33675039, 33206405; Phenotypes: {Macular degeneration, age-related, 8} MIM#613778; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14047 FHL1 Bryony Thompson Gene: fhl1 has been classified as Green List (High Evidence).
Mendeliome v0.14047 FHL1 Bryony Thompson Phenotypes for gene: FHL1 were changed from to Reducing body myopathy MONDO:0019948; X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680
Mendeliome v0.14046 ASPA Elena Savva Phenotypes for gene: ASPA were changed from to Canavan disease MIM#271900; disorder of amino acid metabolism
Mendeliome v0.14045 ASPA Elena Savva Gene: aspa has been classified as Green List (High Evidence).
Mendeliome v0.14045 ASPA Elena Savva Publications for gene: ASPA were set to
Mendeliome v0.14045 ASPA Elena Savva Mode of inheritance for gene: ASPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14044 ASPA Elena Savva reviewed gene: ASPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Canavan disease MIM#271900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14044 ARMS2 Elena Savva Phenotypes for gene: ARMS2 were changed from {Macular degeneration, age-related, 8} MIM#613778 to {Macular degeneration, age-related, 8} MIM#613778
Mendeliome v0.14043 FHL1 Bryony Thompson Publications for gene: FHL1 were set to
Mendeliome v0.14042 FHL1 Bryony Thompson Mode of inheritance for gene: FHL1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.14041 ASH1L Elena Savva Phenotypes for gene: ASH1L were changed from Mental retardation, autosomal dominant 52, MIM#617796 to Mental retardation, autosomal dominant 52, MIM#617796
Mendeliome v0.14041 ASH1L Elena Savva Publications for gene: ASH1L were set to 23033978; 25961944; 28394464; 28191889; 27824329
Mendeliome v0.14040 ARMS2 Elena Savva Phenotypes for gene: ARMS2 were changed from to {Macular degeneration, age-related, 8} MIM#613778
Mendeliome v0.14040 ARMS2 Elena Savva Classified gene: ARMS2 as Red List (low evidence)
Mendeliome v0.14040 ARMS2 Elena Savva Gene: arms2 has been classified as Red List (Low Evidence).
Mendeliome v0.14039 ARMS2 Elena Savva Gene: arms2 has been classified as Green List (High Evidence).
Mendeliome v0.14039 FHL1 Bryony Thompson reviewed gene: FHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19716112, 20186852, 20301609, 18179901, 25274776, 34366191, 18274675, 19181672; Phenotypes: Reducing body myopathy MONDO:0019948, X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.14039 ASH1L Elena Savva Phenotypes for gene: ASH1L were changed from to Mental retardation, autosomal dominant 52, MIM#617796
Mendeliome v0.14038 ASH1L Elena Savva Publications for gene: ASH1L were set to
Mendeliome v0.14038 ASH1L Elena Savva Gene: ash1l has been classified as Green List (High Evidence).
Mendeliome v0.14038 ASH1L Elena Savva Mode of inheritance for gene: ASH1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14037 ARMS2 Elena Savva reviewed gene: ARMS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Macular degeneration, age-related, 8} MIM#613778; Mode of inheritance: Unknown
Mendeliome v0.14037 ARL2BP Elena Savva Publications for gene: ARL2BP were set to PMID: 23849777; 27790702; 29718757
Mendeliome v0.14036 ARL2BP Elena Savva Publications for gene: ARL2BP were set to
Mendeliome v0.14035 ARL2BP Elena Savva Gene: arl2bp has been classified as Green List (High Evidence).
Mendeliome v0.14035 ARL2BP Elena Savva Phenotypes for gene: ARL2BP were changed from to Retinitis pigmentosa with or without situs inversus MIM#615434
Mendeliome v0.14035 ARL2BP Elena Savva Mode of inheritance for gene: ARL2BP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14034 ARL2BP Elena Savva reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa with or without situs inversus MIM#615434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14034 FH Bryony Thompson Gene: fh has been classified as Green List (High Evidence).
Mendeliome v0.14034 FH Bryony Thompson Phenotypes for gene: FH were changed from to hereditary leiomyomatosis and renal cell cancer MONDO:0007888; fumaric aciduria MONDO:0011730
Mendeliome v0.14033 FH Bryony Thompson Publications for gene: FH were set to
Mendeliome v0.14032 FH Bryony Thompson Mode of inheritance for gene: FH was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14031 FH Bryony Thompson changed review comment from: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.; to: Well established gene-disease associations. Loss of function is the mechanism of disease. Monoallelic variants associated with decreased fumarate hydratase enzyme activity cause FH tumour predisposition syndrome (also known as HLRCC; PMID: 11865300, 28300276, 20301430). FH deficiency (also known as fumarase deficiency or fumaric aciduria) caused by biallelic variants results in severe neonatal and early infantile encephalopathy (PMID: 8200987, 20549362, 31746132, 20301679). FH encodes for both mitochondrial and cytosolic FH enzyme isoforms, which catalyze hydration of fumarate to malate.
Mendeliome v0.14031 FH Bryony Thompson edited their review of gene: FH: Changed publications: 11865300, 28300276, 20301430, 8200987, 20549362, 31746132, 20301679
Mendeliome v0.14031 FH Bryony Thompson reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: 11865300, 28300276, 8200987, 20549362, 31746132; Phenotypes: hereditary leiomyomatosis and renal cell cancer MONDO:0007888, fumaric aciduria MONDO:0011730; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.14031 ARID1B Elena Savva Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1 MIM#135900
Mendeliome v0.14030 ARID1B Elena Savva Gene: arid1b has been classified as Green List (High Evidence).
Mendeliome v0.14030 ARID1B Elena Savva Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14029 ARID1B Elena Savva reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 1 MIM#135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.14029 FGG Bryony Thompson Gene: fgg has been classified as Green List (High Evidence).
Mendeliome v0.14029 FGG Bryony Thompson Phenotypes for gene: FGG were changed from to congenital fibrinogen deficiency MONDO:0018060
Mendeliome v0.14028 FGG Bryony Thompson Publications for gene: FGG were set to
Mendeliome v0.14027 ARHGDIA Elena Savva Phenotypes for gene: ARHGDIA were changed from Nephrotic syndrome, type 8 MIM#615244 to Nephrotic syndrome, type 8 MIM#615244
Mendeliome v0.14026 ARHGDIA Elena Savva Publications for gene: ARHGDIA were set to PMID: 23867502; 35060086
Mendeliome v0.14026 ARHGDIA Elena Savva Mode of inheritance for gene: ARHGDIA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14025 ARHGEF18 Elena Savva Gene: arhgef18 has been classified as Green List (High Evidence).
Mendeliome v0.14025 FGG Bryony Thompson Mode of inheritance for gene: FGG was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14024 FGG Bryony Thompson reviewed gene: FGG: Rating: GREEN; Mode of pathogenicity: None; Publications: 2713997, 11001902, 11001903, 9746756, 23560673, 28992465, 10980108, 15304068; Phenotypes: congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.14024 FGFR3 Bryony Thompson Phenotypes for gene: FGFR3 were changed from achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833 to achondroplasia MONDO:0007037; Thanatophoric dysplasia type 1 MONDO:0008546; Thanatophoric dysplasia type 2 MONDO:0008547; hypochondroplasia MONDO:0007793; Muenke syndrome MONDO:0011274; FGFR3-related chondrodysplasia MONDO:0019685; severe achondroplasia-developmental delay-acanthosis nigricans syndrome MONDO:0014658; Crouzon syndrome-acanthosis nigricans syndrome MONDO:0012833; camptodactyly-tall stature-scoliosis-hearing loss syndrome MONDO:0012504
Mendeliome v0.14023 FGFR3 Bryony Thompson Publications for gene: FGFR3 were set to 26740388; 20301331; 20301540; 20301650; 20301628; 24864036; 17033969
Mendeliome v0.14022 FGFR3 Bryony Thompson Mode of pathogenicity for gene: FGFR3 was changed from to Other
Mendeliome v0.14021 FGFR3 Bryony Thompson Mode of inheritance for gene: FGFR3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14020 FGFR3 Bryony Thompson changed review comment from: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome where bialellic loss-of-function is the expected mechanism of disease. Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome.; to: FGFR3 has many well-established gene-disease associations with various skeletal dysplasia phenotypes. Gain-of-function is the main mechanism of disease for these disorders, except camptodactyly-tall stature-scoliosis-hearing loss syndrome (CATSHL syndrome, see separate curation below). Specific monoallelic variants cause different phenotypes: >99% achondroplasia is caused by variants leading to the missense change p.Gly380Arg; Cysteine substitutions and stop-loss protein elongation variants are highly specific for Thanatophoric dysplasia (TD) type 1; p.Lys650Glu is associated with TD type 2; p.Ala391Glu causes Crouzon syndrome with acanthosis nigricans; and p.Pro250Arg causes Muenke syndrome.
Moderate evidence for CATSHL syndrome, AD & AR: PMID: 8630492, 17033969, 27139183, 24864036, 32641982 - 2 apparently unrelated families segregating the same missense, p.Arg621His. One consanguineous family with 2 affected brothers with homozygous p.Thr546Lys. Heterozygous individuals in the family were unaffected. No functional assays were conducted for either missense to demonstrate loss of function. Null mouse and zebrafish models are similar to the human CATSHL syndrome phenotype.
Mendeliome v0.14020 GUCA1B Zornitza Stark changed review comment from: Single founder variant identified in several Japanese individuals.; to: Single founder variant identified in several Japanese individuals.

No other P/LP variants in ClinVar.
Mendeliome v0.14020 GUCA1B Zornitza Stark Gene: guca1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14020 GUCA1B Zornitza Stark Phenotypes for gene: GUCA1B were changed from to Retinitis pigmentosa 48, MIM# 613827
Mendeliome v0.14019 GUCA1B Zornitza Stark Publications for gene: GUCA1B were set to
Mendeliome v0.14018 GUCA1B Zornitza Stark Mode of inheritance for gene: GUCA1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.14017 GUCA1B Zornitza Stark Classified gene: GUCA1B as Amber List (moderate evidence)