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| Mendeliome v1.1111 | NEB | Achchuthan Shanmugasundram reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 12207937, 21798101, 33376055, 37010288; Phenotypes: Arthrogryposis multiplex congenita 6, OMIM:619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9776 | NEBL | Bryony Thompson Classified gene: NEBL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9776 | NEBL | Bryony Thompson Added comment: Comment on list classification: Limited gene-disease vailidity, Classification - 09/25/2020 by ClinGen Dilated Cardiomyopathy GCEP. Evidence Summary: NEBL was evaluated for autosomal dominant dilated cardiomyopathy (DCM). Human genetic evidence supporting this gene-disease relationship includes case-level data. Arimura and colleagues (2000, PMID: 11140941) analyzed 83 DCM patients and 311 healthy controls, identifying 4 missense variants of unknown significance (VUSs) in 4 DCM cases. High minor allele frequencies (MAFs) and lack of segregation excluded these variants as evidence. Purevjav and colleagues (2010, PMID: 20951326) investigated a total of 260 DCM patients and 300 unrelated ethnic matched controls by direct DNA sequencing. Authors identified 4 missense VUSs. One of these variants (Q128R) was downgraded in level of evidence due to the lack of segregation. The other 3 variants were not scored because of their MAF. Perrot and colleagues (2016, PMID: 27186169) investigated a total of 389 patients with DCM, HCM, or LVNC, 320 Caucasian sex-matched controls and 192 Caucasian sex-matched blood donors and identified 3 missense VUSs in 4 families. One of these variants was also carried by healthy relatives and therefore was excluded, however this may be explained by reduced penetrance. The 2 other variants lacked segregation as well and therefore were also excluded. In addition, this gene-disease association is supported by animal models. Mastronotaro and colleagues (2015, PMID: 25987543) created a NEBL knockout mice that exhibited normal cardiac function up to 9 months of age but after 2 weeks of transaortic constriction (TAC), these mice showed Z-line widening since the age of 5 months and upregulation of cardiac stress genes (basal and after TAC) However, absence of clinical DCM features in KO-NEBL mice as well as Western Blot analysis which contradicted previous findings by showing a similar protein expression between knockout and wild-type mice, excluding it as evidence. Purevjav and colleagues (2010, PMID: 20951326) generated a transgenic mouse overexpressing WT or mutant NEBL under the control of the α-MyHC promoter (4 variants were tested). Mice overexpressing p.K60N or p.Q128R variants died within 1 year because of severe heart enlargement and heart failure. Mice overexpressing p.G202R or p.A592E were born and developed normally but after 6 months displayed reduced stress tolerance, cardiac enlargement due to left ventricle dilation, myocyte disarray, and interstitial cell infiltration. In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of NEBL and autosomal dominant DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on October 11, 2019 (SOP Version 7). Gene Clinical Validity Standard Operating Procedures (SOP) - SOP7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9776 | NEBL | Bryony Thompson Gene: nebl has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7737 | NEB | Zornitza Stark Publications for gene: NEB were set to 25205138 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7736 | NEB | Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy 2, autosomal recessive 256030 to Nemaline myopathy 2, autosomal recessive 256030; MONDO:0009725; Arthrogryposis multiplex congenita 6, MIM# 619334 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7735 | NEB | Zornitza Stark reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051637, 22367672, 26578207, 33376055; Phenotypes: Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4141 | TIMM8A | Zornitza Stark Phenotypes for gene: TIMM8A were changed from to Mohr-Tranebjaerg syndrome, MIM# 304700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4139 | TIMM8A | Zornitza Stark reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 11803487, 11405816; Phenotypes: Mohr-Tranebjaerg syndrome, MIM# 304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3287 | NEB | Zornitza Stark Marked gene: NEB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3287 | NEB | Zornitza Stark Gene: neb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3287 | NEB | Zornitza Stark Phenotypes for gene: NEB were changed from to Nemaline myopathy 2, autosomal recessive 256030 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3286 | NEB | Zornitza Stark Publications for gene: NEB were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3285 | NEB | Zornitza Stark Mode of inheritance for gene: NEB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3281 | NEB | Elena Savva reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25205138; Phenotypes: Nemaline myopathy 2, autosomal recessive 256030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2253 | NEBL | Zornitza Stark Marked gene: NEBL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2253 | NEBL | Zornitza Stark Gene: nebl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2253 | NEBL | Zornitza Stark Phenotypes for gene: NEBL were changed from to Hypertrophic cardiomyopathy; dilated cardiomyopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2252 | NEBL | Zornitza Stark Publications for gene: NEBL were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2251 | NEBL | Zornitza Stark Mode of inheritance for gene: NEBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | NEBL |
Zornitza Stark gene: NEBL was added gene: NEBL was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: NEBL was set to Unknown |
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| Mendeliome v0.0 | NEB |
Zornitza Stark gene: NEB was added gene: NEB was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: NEB was set to Unknown |
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