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Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Tag disputed tag was added to gene: TCAP.
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Added comment: Comment on list classification: Now DISPUTED gene-disease association by ClinGen Hereditary Cardiovascular Disease GCEP
Hypertrophic cardiomyopathy_HCM v0.178 TCAP Bryony Thompson Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Marked gene: CORIN as ready
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Classified gene: CORIN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.177 CORIN Seb Lunke Gene: corin has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.176 CORIN Daniel Flanagan gene: CORIN was added
gene: CORIN was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: CORIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CORIN were set to 37913506; 15637153
Phenotypes for gene: CORIN were set to ?Cardiomyopathy, familial hypertrophic, 30, atrial (MIM:620734)
Review for gene: CORIN was set to RED
Added comment: Two siblings with a homozygous loss-of-function variant in CORIN. Both presented with left atrial hypertrophic cardiomyopathy, hypertension, fibrosis, and arrhythmia isolated to the left atrium. A plasma sample obtained from one of the siblings had no detectable levels of corin.

One sibling also had a het variant, p.(Ser571Thr), in PKP2 (associated with AD ARVC). The PKP2 variant is LP/VUS in ClinVar.

Cor-/- mice exhibit cardiac hypertrophy resulting in a mild decline in cardiac function later in life. Cor-/- mice also have spontaneous hypertension.
Sources: Expert list
Hypertrophic cardiomyopathy_HCM v0.176 TTR Zornitza Stark Tag treatable tag was added to gene: TTR.
Hypertrophic cardiomyopathy_HCM v0.176 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to 26846950; 27106955; 32480058
Hypertrophic cardiomyopathy_HCM v0.175 ALPK3 Sarah Pantaleo reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34263907, 35783621; Phenotypes: Cardiomyopathy, familial hypertrophic 27 MIM#618052; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.175 CACNA1C Zornitza Stark Phenotypes for gene: CACNA1C were changed from Hypertrophic cardiomyopathy; congenital heart defects; conduction abnormalities to Hypertrophic cardiomyopathy, MONDO:0005045, CACNA1C-related
Hypertrophic cardiomyopathy_HCM v0.174 CACNA1C Zornitza Stark Classified gene: CACNA1C as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.174 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.173 CACNA1C Zornitza Stark edited their review of gene: CACNA1C: Added comment: Evidence only of association of a specific missense with HCM.; Changed rating: AMBER
Hypertrophic cardiomyopathy_HCM v0.173 ACTN2 Zornitza Stark Classified gene: ACTN2 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.173 ACTN2 Zornitza Stark Gene: actn2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.172 ACTN2 Zornitza Stark reviewed gene: ACTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.172 KLHL24 Zornitza Stark Phenotypes for gene: KLHL24 were changed from Hypertrophic cardiomyopathy to Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, MIM# 620236
Hypertrophic cardiomyopathy_HCM v0.171 Zornitza Stark HPO terms changed from to Hypertrophic cardiomyopathy, HP:0001639
List of related panels changed from to Hypertrophic cardiomyopathy; HP:0001639
Hypertrophic cardiomyopathy_HCM v0.170 RPS6KB1 Zornitza Stark Marked gene: RPS6KB1 as ready
Hypertrophic cardiomyopathy_HCM v0.170 RPS6KB1 Zornitza Stark Gene: rps6kb1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.170 RPS6KB1 Zornitza Stark Classified gene: RPS6KB1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.170 RPS6KB1 Zornitza Stark Gene: rps6kb1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.169 RPS6KB1 Zornitza Stark gene: RPS6KB1 was added
gene: RPS6KB1 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: RPS6KB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS6KB1 were set to 34916228
Phenotypes for gene: RPS6KB1 were set to Hypertrophic cardiomyopathy, MONDO:0005045, RPS6KB1-related
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
Hypertrophic cardiomyopathy_HCM v0.168 DNAJB4 Zornitza Stark Marked gene: DNAJB4 as ready
Hypertrophic cardiomyopathy_HCM v0.168 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.168 DNAJB4 Zornitza Stark Classified gene: DNAJB4 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.168 DNAJB4 Zornitza Stark Gene: dnajb4 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.167 DNAJB4 Karina Sandoval gene: DNAJB4 was added
gene: DNAJB4 was added to Hypertrophic cardiomyopathy_HCM. 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 RED
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.

Only one had HCM.

Functional studies including mouse model.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.167 FHOD3 Zornitza Stark Publications for gene: FHOD3 were set to 32335906; 31742804; 30442288
Hypertrophic cardiomyopathy_HCM v0.166 FHOD3 Chern Lim reviewed gene: FHOD3: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32335906, 33586461, 30442288, 28991257; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.166 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
Hypertrophic cardiomyopathy_HCM v0.165 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
Hypertrophic cardiomyopathy_HCM v0.165 TULP3 Alison Yeung Classified gene: TULP3 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.165 TULP3 Alison Yeung Gene: tulp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.164 TULP3 Anna Ritchie Deleted their comment
Hypertrophic cardiomyopathy_HCM v0.164 TULP3 Anna Ritchie Deleted their comment
Hypertrophic cardiomyopathy_HCM v0.164 TULP3 Alison Yeung Classified gene: TULP3 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.164 TULP3 Alison Yeung Gene: tulp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.163 TULP3 Anna Ritchie commented on gene: TULP3: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy.

The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals.
Hypertrophic cardiomyopathy_HCM v0.163 TULP3 Anna Ritchie edited their review of gene: TULP3: Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy.

The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals.; Changed rating: GREEN
Hypertrophic cardiomyopathy_HCM v0.163 TULP3 Alison Yeung Classified gene: TULP3 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.163 TULP3 Alison Yeung Gene: tulp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.162 TULP3 Alison Yeung Marked gene: TULP3 as ready
Hypertrophic cardiomyopathy_HCM v0.162 TULP3 Alison Yeung Gene: tulp3 has been removed from the panel.
Hypertrophic cardiomyopathy_HCM v0.162 TULP3 Anna Ritchie gene: TULP3 was added
gene: TULP3 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045
Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis with variable fibrocystic kidney disease and hypertrophic cardiomyopathy.

The human phenotype was ecapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.162 TRIM63 Zornitza Stark Phenotypes for gene: TRIM63 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v0.161 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy, MONDO:0005045
Hypertrophic cardiomyopathy_HCM v0.160 GYG1 Zornitza Stark Marked gene: GYG1 as ready
Hypertrophic cardiomyopathy_HCM v0.160 GYG1 Zornitza Stark Gene: gyg1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.160 GYG1 Zornitza Stark Classified gene: GYG1 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.160 GYG1 Zornitza Stark Gene: gyg1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.159 GYG1 Zornitza Stark gene: GYG1 was added
gene: GYG1 was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert Review
Mode of inheritance for gene: GYG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GYG1 were set to 27718144; 20357282; 31628455
Phenotypes for gene: GYG1 were set to Hypertrophic Cardiomyopathy
Review for gene: GYG1 was set to AMBER
Added comment: 4 unrelated patients described in these reports with homozygous/compound het mutations in GYG1. All had a form of HCM, with extensive scarring, arrhythmia. Histological studies reveal storage of glycogen & polyglycosan associated with mutated glycogenin 1 within cardiac myocytes. The 3 patients in PMID 27718144 did not have overt skeletal myopathy. Other patients with mutations in this gene have had skeletal myopathy without cardiomyopathy. The cause for this variable expression is not entirely clear. The sister of one patient carried the homozygous mutation, but was asymptomatic.

Well established gene-disease association with glycogen storage disorder, primarily affecting skeletal muscle.
Sources: Expert Review
Hypertrophic cardiomyopathy_HCM v0.158 NEBL Bryony Thompson Classified gene: NEBL as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.158 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
Hypertrophic cardiomyopathy_HCM v0.158 NEBL Bryony Thompson Gene: nebl has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.157 OBSCN Zornitza Stark Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914
Hypertrophic cardiomyopathy_HCM v0.156 OBSCN Zornitza Stark reviewed gene: OBSCN: Rating: RED; Mode of pathogenicity: None; Publications: 33438037; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.156 FHOD3 Zornitza Stark Phenotypes for gene: FHOD3 were changed from Hypertrophic cardiomyopathy to Cardiomyopathy, familial hypertrophic, 28, MIM# 619402
Hypertrophic cardiomyopathy_HCM v0.155 FHOD3 Zornitza Stark reviewed gene: FHOD3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, familial hypertrophic, 28, MIM# 619402; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.153 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Hypertrophic cardiomyopathy_HCM v0.152 GAA Zornitza Stark Phenotypes for gene: GAA were changed from to Glycogen storage disease II, MIM#232300
Hypertrophic cardiomyopathy_HCM v0.151 GAA Zornitza Stark Publications for gene: GAA were set to
Hypertrophic cardiomyopathy_HCM v0.150 GAA Zornitza Stark Mode of inheritance for gene: GAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.149 FHL1 Zornitza Stark Marked gene: FHL1 as ready
Hypertrophic cardiomyopathy_HCM v0.149 FHL1 Zornitza Stark Gene: fhl1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.149 FHL1 Zornitza Stark Classified gene: FHL1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.149 FHL1 Zornitza Stark Gene: fhl1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.148 FHL1 Zornitza Stark gene: FHL1 was added
gene: FHL1 was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FHL1 were set to Emery-Dreifuss muscular dystrophy 6, X-linked, MIM# 300696
Review for gene: FHL1 was set to GREEN
Added comment: HCM is part of the phenotype.
Sources: Expert list
Hypertrophic cardiomyopathy_HCM v0.147 CACNA1C Zornitza Stark Marked gene: CACNA1C as ready
Hypertrophic cardiomyopathy_HCM v0.147 CACNA1C Zornitza Stark Gene: cacna1c has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.147 CACNA1C Zornitza Stark gene: CACNA1C was added
gene: CACNA1C was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert list
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1C were set to 26253506; 28490369; 28866666
Phenotypes for gene: CACNA1C were set to Hypertrophic cardiomyopathy; congenital heart defects; conduction abnormalities
Review for gene: CACNA1C was set to RED
Added comment: Recurrent missense at position p.Arg518Cys/His observed in three families with complex cardiac phenotype including HCM. Digenic/trigenic inheritance postulated in other families.
Sources: Expert list
Hypertrophic cardiomyopathy_HCM v0.146 GLA Zornitza Stark changed review comment from: HOCM can be a presenting feature of Fabry.; to: HCM can be a presenting feature of Fabry.
Hypertrophic cardiomyopathy_HCM v0.146 MYH6 Zornitza Stark Marked gene: MYH6 as ready
Hypertrophic cardiomyopathy_HCM v0.146 MYH6 Zornitza Stark Gene: myh6 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.146 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.145 MYH6 Zornitza Stark Publications for gene: MYH6 were set to
Hypertrophic cardiomyopathy_HCM v0.144 MYH6 Zornitza Stark Mode of inheritance for gene: MYH6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.143 MYH6 Zornitza Stark Classified gene: MYH6 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.143 MYH6 Zornitza Stark Gene: myh6 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.142 PLN Seb Lunke Marked gene: PLN as ready
Hypertrophic cardiomyopathy_HCM v0.142 PLN Seb Lunke Gene: pln has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.142 PRKAG2 Zornitza Stark Marked gene: PRKAG2 as ready
Hypertrophic cardiomyopathy_HCM v0.142 PRKAG2 Zornitza Stark Gene: prkag2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.142 PRKAG2 Zornitza Stark Phenotypes for gene: PRKAG2 were changed from Cardiomyopathy, hypertrophic 6, MIM# 600858 to Cardiomyopathy, hypertrophic 6, MIM# 600858
Hypertrophic cardiomyopathy_HCM v0.142 PLN Seb Lunke Phenotypes for gene: PLN were changed from to Cardiomyopathy, hypertrophic, 18 (MIM #613874)
Hypertrophic cardiomyopathy_HCM v0.141 PLN Seb Lunke Publications for gene: PLN were set to
Hypertrophic cardiomyopathy_HCM v0.141 PRKAG2 Zornitza Stark Phenotypes for gene: PRKAG2 were changed from to Cardiomyopathy, hypertrophic 6, MIM# 600858
Hypertrophic cardiomyopathy_HCM v0.140 PRKAG2 Zornitza Stark Publications for gene: PRKAG2 were set to
Hypertrophic cardiomyopathy_HCM v0.139 PRKAG2 Zornitza Stark Mode of inheritance for gene: PRKAG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.138 PRKAG2 Zornitza Stark reviewed gene: PRKAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, hypertrophic 6, MIM# 600858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.138 PLN Seb Lunke Mode of inheritance for gene: PLN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy_HCM v0.137 LAMP2 Zornitza Stark Marked gene: LAMP2 as ready
Hypertrophic cardiomyopathy_HCM v0.137 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.137 LAMP2 Zornitza Stark Phenotypes for gene: LAMP2 were changed from to Danon disease (MIM#300257)
Hypertrophic cardiomyopathy_HCM v0.136 LAMP2 Zornitza Stark Publications for gene: LAMP2 were set to
Hypertrophic cardiomyopathy_HCM v0.135 LAMP2 Zornitza Stark Mode of inheritance for gene: LAMP2 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)
Hypertrophic cardiomyopathy_HCM v0.134 LAMP2 Zornitza Stark reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Danon disease (MIM#300257); Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v0.134 TTR Seb Lunke Marked gene: TTR as ready
Hypertrophic cardiomyopathy_HCM v0.134 TTR Seb Lunke Added comment: Comment when marking as ready: Can present predominantly with HCM
Hypertrophic cardiomyopathy_HCM v0.134 TTR Seb Lunke Gene: ttr has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.134 TTR Seb Lunke Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related MIM#105210
Hypertrophic cardiomyopathy_HCM v0.133 TTR Seb Lunke Publications for gene: TTR were set to
Hypertrophic cardiomyopathy_HCM v0.132 GLA Zornitza Stark Phenotypes for gene: GLA were changed from Fabry disease (MIM# 301500) to Fabry disease (MIM# 301500)
Hypertrophic cardiomyopathy_HCM v0.131 GLA Zornitza Stark Marked gene: GLA as ready
Hypertrophic cardiomyopathy_HCM v0.131 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.131 TTR Seb Lunke Mode of inheritance for gene: TTR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.131 GLA Zornitza Stark Phenotypes for gene: GLA were changed from to Fabry disease (MIM# 301500)
Hypertrophic cardiomyopathy_HCM v0.130 GLA Zornitza Stark Publications for gene: GLA were set to
Hypertrophic cardiomyopathy_HCM v0.130 GLA Zornitza Stark Mode of inheritance for gene: GLA 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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypertrophic cardiomyopathy_HCM v0.129 GLA Zornitza Stark Mode of inheritance for gene: GLA 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)
Hypertrophic cardiomyopathy_HCM v0.128 GLA Zornitza Stark reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fabry disease (MIM# 301500); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypertrophic cardiomyopathy_HCM v0.128 GAA Seb Lunke Marked gene: GAA as ready
Hypertrophic cardiomyopathy_HCM v0.128 GAA Seb Lunke Gene: gaa has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.128 GAA Seb Lunke Classified gene: GAA as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.128 GAA Seb Lunke Gene: gaa has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.127 FXN Zornitza Stark Marked gene: FXN as ready
Hypertrophic cardiomyopathy_HCM v0.127 FXN Zornitza Stark Gene: fxn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.127 FXN Zornitza Stark Phenotypes for gene: FXN were changed from to Friedreich ataxia MIM#229300
Hypertrophic cardiomyopathy_HCM v0.126 FXN Zornitza Stark Mode of inheritance for gene: FXN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.125 FXN Zornitza Stark Classified gene: FXN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.125 FXN Zornitza Stark Gene: fxn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.124 SLC25A4 Zornitza Stark Marked gene: SLC25A4 as ready
Hypertrophic cardiomyopathy_HCM v0.124 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.124 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 MIM#609283 to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 MIM#609283
Hypertrophic cardiomyopathy_HCM v0.124 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 MIM#609283
Hypertrophic cardiomyopathy_HCM v0.123 SLC25A4 Zornitza Stark Publications for gene: SLC25A4 were set to
Hypertrophic cardiomyopathy_HCM v0.122 SLC25A4 Zornitza Stark Mode of inheritance for gene: SLC25A4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.121 MT-TI Seb Lunke Marked gene: MT-TI as ready
Hypertrophic cardiomyopathy_HCM v0.121 MT-TI Seb Lunke Added comment: Comment when marking as ready: NOTE: Mitochondrial DNA gene not tractable by many commonly used genomics methods.
Hypertrophic cardiomyopathy_HCM v0.121 MT-TI Seb Lunke Gene: mt-ti has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.121 SLC25A4 Zornitza Stark Classified gene: SLC25A4 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.121 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.120 MT-TI Seb Lunke Classified gene: MT-TI as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.120 MT-TI Seb Lunke Gene: mt-ti has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.119 MT-TI Seb Lunke Tag mtDNA tag was added to gene: MT-TI.
Hypertrophic cardiomyopathy_HCM v0.119 TTN Zornitza Stark Marked gene: TTN as ready
Hypertrophic cardiomyopathy_HCM v0.119 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.119 TTN Zornitza Stark Phenotypes for gene: TTN were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.118 TTN Zornitza Stark Publications for gene: TTN were set to
Hypertrophic cardiomyopathy_HCM v0.117 TTN Zornitza Stark Classified gene: TTN as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.117 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.116 TTN Zornitza Stark Mode of inheritance for gene: TTN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.115 FHOD3 Seb Lunke Marked gene: FHOD3 as ready
Hypertrophic cardiomyopathy_HCM v0.115 FHOD3 Seb Lunke Gene: fhod3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.115 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from Noonan syndrome 1 MIM# 163950 to Noonan syndrome 1 MIM# 163950
Hypertrophic cardiomyopathy_HCM v0.114 FHOD3 Seb Lunke Tag SV/CNV tag was added to gene: FHOD3.
Hypertrophic cardiomyopathy_HCM v0.114 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Hypertrophic cardiomyopathy_HCM v0.114 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.114 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from to Noonan syndrome 1 MIM# 163950
Hypertrophic cardiomyopathy_HCM v0.114 FHOD3 Seb Lunke Classified gene: FHOD3 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.114 FHOD3 Seb Lunke Gene: fhod3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.113 PTPN11 Zornitza Stark Mode of inheritance for gene: PTPN11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.112 PTPN11 Zornitza Stark Classified gene: PTPN11 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.112 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.111 OBSCN Paul De Fazio Deleted their comment
Hypertrophic cardiomyopathy_HCM v0.111 OBSCN Paul De Fazio commented on gene: OBSCN: Limited evidence by ClinGen working group.

Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review).

No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically.
Hypertrophic cardiomyopathy_HCM v0.111 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Hypertrophic cardiomyopathy_HCM v0.111 RAF1 Zornitza Stark Gene: raf1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.111 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from to Cardiomyopathy, dilated, 1NN MIM#615916; Noonan syndrome 5 MIM#611553
Hypertrophic cardiomyopathy_HCM v0.110 RAF1 Zornitza Stark Publications for gene: RAF1 were set to
Hypertrophic cardiomyopathy_HCM v0.109 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.109 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.108 RAF1 Zornitza Stark Classified gene: RAF1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.108 RAF1 Zornitza Stark Gene: raf1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.107 OBSCN Zornitza Stark Marked gene: OBSCN as ready
Hypertrophic cardiomyopathy_HCM v0.107 OBSCN Zornitza Stark Gene: obscn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.107 OBSCN Zornitza Stark Classified gene: OBSCN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.107 OBSCN Zornitza Stark Gene: obscn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.106 PDLIM3 Zornitza Stark Marked gene: PDLIM3 as ready
Hypertrophic cardiomyopathy_HCM v0.106 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.106 PDLIM3 Zornitza Stark Classified gene: PDLIM3 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.106 PDLIM3 Zornitza Stark Gene: pdlim3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Marked gene: RYR2 as ready
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Added comment: Comment when marking as ready: Gene is associated with CPVT phenotype.
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Gene: ryr2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Classified gene: RYR2 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Gene: ryr2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Classified gene: RYR2 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.105 RYR2 Zornitza Stark Gene: ryr2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.104 MYPN Zornitza Stark Marked gene: MYPN as ready
Hypertrophic cardiomyopathy_HCM v0.104 MYPN Zornitza Stark Gene: mypn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.104 MYPN Zornitza Stark Classified gene: MYPN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.104 MYPN Zornitza Stark Gene: mypn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.103 TRIM63 Zornitza Stark Marked gene: TRIM63 as ready
Hypertrophic cardiomyopathy_HCM v0.103 TRIM63 Zornitza Stark Gene: trim63 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.103 TRIM63 Zornitza Stark Classified gene: TRIM63 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.103 TRIM63 Zornitza Stark Gene: trim63 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.102 MYOZ2 Zornitza Stark Marked gene: MYOZ2 as ready
Hypertrophic cardiomyopathy_HCM v0.102 MYOZ2 Zornitza Stark Gene: myoz2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.102 MYOZ2 Zornitza Stark Phenotypes for gene: MYOZ2 were changed from to Cardiomyopathy, hypertrophic, 16 MIM#613838
Hypertrophic cardiomyopathy_HCM v0.101 MYOZ2 Zornitza Stark Publications for gene: MYOZ2 were set to
Hypertrophic cardiomyopathy_HCM v0.100 MYOZ2 Zornitza Stark Mode of inheritance for gene: MYOZ2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.99 MYOZ2 Zornitza Stark Classified gene: MYOZ2 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.99 MYOZ2 Zornitza Stark Gene: myoz2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.98 JPH2 Zornitza Stark Marked gene: JPH2 as ready
Hypertrophic cardiomyopathy_HCM v0.98 JPH2 Zornitza Stark Added comment: Comment when marking as ready: Note one of the variants p.Gly505Ser is present in >500 individuals in gnomad, including 7 homozygotes.
Hypertrophic cardiomyopathy_HCM v0.98 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.98 JPH2 Zornitza Stark Phenotypes for gene: JPH2 were changed from to Cardiomyopathy, hypertrophic, MIM#613873
Hypertrophic cardiomyopathy_HCM v0.97 JPH2 Zornitza Stark Publications for gene: JPH2 were set to
Hypertrophic cardiomyopathy_HCM v0.96 JPH2 Zornitza Stark Mode of inheritance for gene: JPH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.95 JPH2 Zornitza Stark Classified gene: JPH2 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.95 JPH2 Zornitza Stark Gene: jph2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.94 KLF10 Zornitza Stark Marked gene: KLF10 as ready
Hypertrophic cardiomyopathy_HCM v0.94 KLF10 Zornitza Stark Gene: klf10 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.94 KLF10 Zornitza Stark Classified gene: KLF10 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.94 KLF10 Zornitza Stark Gene: klf10 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.93 TNNC1 Zornitza Stark Marked gene: TNNC1 as ready
Hypertrophic cardiomyopathy_HCM v0.93 TNNC1 Zornitza Stark Gene: tnnc1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.93 TNNC1 Zornitza Stark Phenotypes for gene: TNNC1 were changed from to Cardiomyopathy, hypertrophic, 13 (MIM# 613243)
Hypertrophic cardiomyopathy_HCM v0.92 TNNC1 Zornitza Stark Publications for gene: TNNC1 were set to
Hypertrophic cardiomyopathy_HCM v0.91 TNNC1 Zornitza Stark Mode of inheritance for gene: TNNC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.90 TNNC1 Zornitza Stark Classified gene: TNNC1 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.90 TNNC1 Zornitza Stark Gene: tnnc1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.89 PRKAG2 Ain Roesley reviewed gene: PRKAG2: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: PRKAG2-cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy_HCM v0.89 PLN Ain Roesley reviewed gene: PLN: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy_HCM v0.89 LAMP2 Ain Roesley reviewed gene: LAMP2: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: Danon disease (MIM#300257); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypertrophic cardiomyopathy_HCM v0.89 TTR Paul De Fazio reviewed gene: TTR: Rating: AMBER; Mode of pathogenicity: None; Publications: 28475415, 31554435; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 GLA Ain Roesley reviewed gene: GLA: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: Fabry disease (MIM# 301500); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hypertrophic cardiomyopathy_HCM v0.89 GAA Paul De Fazio edited their review of gene: GAA: Set current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 GAA Paul De Fazio reviewed gene: GAA: Rating: RED; Mode of pathogenicity: None; Publications: 27142047; Phenotypes: Glycogen storage disease II MIM#232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.89 FXN Paul De Fazio reviewed gene: FXN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Friedreich ataxia MIM#229300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 SLC25A4 Paul De Fazio changed review comment from: Associated with mitochondrial DNA depletion syndrome for which cardiomyopathy is a feature. Not associated with isolated HCM.; to: Associated with mitochondrial DNA depletion syndrome for which HCM is a feature. Not associated with isolated HCM.
Hypertrophic cardiomyopathy_HCM v0.89 SLC25A4 Paul De Fazio reviewed gene: SLC25A4: Rating: RED; Mode of pathogenicity: None; Publications: 16155110; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 MT-TI Paul De Fazio changed review comment from: PMID: 12767666
2 families with maternally inherited HCM, variants were homoplasmic in tested affecteds (m.4300A>G)

PMID: 30025578
1 family with HCM, variant was homoplasmic (m.4300A>G)

PMID: 29481798
Homoplasmic m.4318-4322delC in one family with DCM and mitochondrial DNA depletion

PMID: 23332932
Describe the morphologic, biochemical, and molecular features of hearts from 3 transplanted patients from 2 families (2x m.4300A>G, 1x m.4277C>T) with HCM.

Seems to be an association with HCM but also possibly DCM? Not sure if this belongs on this panel. The HCM in the literature appears to be isolated.
Sources: Literature; to: PMID: 12767666
2 families with maternally inherited HCM, variants were homoplasmic in tested affecteds (m.4300A>G)

PMID: 30025578
1 family with HCM, variant was homoplasmic (m.4300A>G)

PMID: 29481798
Homoplasmic m.4318-4322delC in one family with DCM and mitochondrial DNA depletion, other mtDNA abnormalities were also identified in this family.

PMID: 23332932
Describe the morphologic, biochemical, and molecular features of hearts from 3 transplanted patients from 2 families (2x m.4300A>G, 1x m.4277C>T) with HCM.

Seems to be an association with HCM but also possibly DCM? Not sure if this belongs on this panel. The HCM in the literature appears to be isolated.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 MT-TI Paul De Fazio edited their review of gene: MT-TI: Changed publications: 12767666, 30025578, 29481798, 23332932
Hypertrophic cardiomyopathy_HCM v0.89 MT-TI Paul De Fazio changed review comment from: PMID: 12767666
2 families with maternally inherited HCM, variants were homoplasmic in tested affecteds (m.4300A>G)

PMID: 30025578
1 family with HCM, variant was homoplasmic (m.4300A>G)

PMID: 29481798
Homoplasmic m.4318-4322delC in one family with DCM and mitochondrial DNA depletion

Seems to be an association with HCM but also DCM and other mito-related phenotypes?
Sources: Literature; to: PMID: 12767666
2 families with maternally inherited HCM, variants were homoplasmic in tested affecteds (m.4300A>G)

PMID: 30025578
1 family with HCM, variant was homoplasmic (m.4300A>G)

PMID: 29481798
Homoplasmic m.4318-4322delC in one family with DCM and mitochondrial DNA depletion

PMID: 23332932
Describe the morphologic, biochemical, and molecular features of hearts from 3 transplanted patients from 2 families (2x m.4300A>G, 1x m.4277C>T) with HCM.

Seems to be an association with HCM but also possibly DCM? Not sure if this belongs on this panel. The HCM in the literature appears to be isolated.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 MT-TI Paul De Fazio gene: MT-TI was added
gene: MT-TI was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene gene: MT-TI was set to MITOCHONDRIAL
Publications for gene: MT-TI were set to 12767666; 30025578; 29481798
Phenotypes for gene: MT-TI were set to Hypertrophic cardiomyopathy
Review for gene: MT-TI was set to AMBER
gene: MT-TI was marked as current diagnostic
Added comment: PMID: 12767666
2 families with maternally inherited HCM, variants were homoplasmic in tested affecteds (m.4300A>G)

PMID: 30025578
1 family with HCM, variant was homoplasmic (m.4300A>G)

PMID: 29481798
Homoplasmic m.4318-4322delC in one family with DCM and mitochondrial DNA depletion

Seems to be an association with HCM but also DCM and other mito-related phenotypes?
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 TTN Dean Phelan reviewed gene: TTN: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 27625337, 31628103; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.89 FHOD3 Ain Roesley changed review comment from: PMID: 32335906;
Deletion of exon 15-16 in 3 families

PMID: 31742804
- 7 affecteds in a 3-generation family, het for p.(Ser527del)
- 1 genotype positive, phenotype negative family member
- 3 other SNVs associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects

PMID: 30442288;
- 60 HCM patients with no other variants in other sarcomeric genes
- segregation of likely path/path variants were definitive/likely in 17 families (4 of which are part of a large pedigree)
Sources: Literature; to: PMID: 32335906;
Deletion of exon 15-16 in 3 families

PMID: 31742804
- 7 affecteds in a 3-generation family, het for p.(Ser527del)
- 1 genotype positive, phenotype negative family member
- 3 other SNVs associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects

PMID: 30442288;
- 60 HCM probands with no other variants in other sarcomeric genes
- segregation of likely path/path variants were definitive/likely in 17 families (4 of which are part of a large pedigree)
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 FHOD3 Ain Roesley gene: FHOD3 was added
gene: FHOD3 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: FHOD3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FHOD3 were set to 32335906; 31742804; 30442288
Phenotypes for gene: FHOD3 were set to Hypertrophic cardiomyopathy
Penetrance for gene: FHOD3 were set to unknown
Review for gene: FHOD3 was set to GREEN
Added comment: PMID: 32335906;
Deletion of exon 15-16 in 3 families

PMID: 31742804
- 7 affecteds in a 3-generation family, het for p.(Ser527del)
- 1 genotype positive, phenotype negative family member
- 3 other SNVs associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects

PMID: 30442288;
- 60 HCM patients with no other variants in other sarcomeric genes
- segregation of likely path/path variants were definitive/likely in 17 families (4 of which are part of a large pedigree)
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 PTPN11 Paul De Fazio reviewed gene: PTPN11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 1 MIM# 163950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 RAF1 Paul De Fazio reviewed gene: RAF1: Rating: RED; Mode of pathogenicity: None; Publications: 24777450; Phenotypes: Cardiomyopathy, dilated, 1NN MIM#615916, Noonan syndrome 5 MIM#611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 OBSCN Paul De Fazio gene: OBSCN was added
gene: OBSCN was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: OBSCN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914
Phenotypes for gene: OBSCN were set to Hypertrophic cardiomyopathy
Review for gene: OBSCN was set to RED
gene: OBSCN was marked as current diagnostic
Added comment: Limited evidence by ClinGen working group.

Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review).

No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 PDLIM3 Ain Roesley gene: PDLIM3 was added
gene: PDLIM3 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: PDLIM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PDLIM3 were set to 30681346; 26455666; 20801532
Phenotypes for gene: PDLIM3 were set to Hypertrophic cardiomyopathy
Penetrance for gene: PDLIM3 were set to unknown
Review for gene: PDLIM3 was set to RED
Added comment: PMID: 30681346;
LIMITED by ClinGen working group

PMID: 26455666;
1x proband with multi-exon deletion

PMID: 20801532;
1x proband het for a missense
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 RYR2 Paul De Fazio gene: RYR2 was added
gene: RYR2 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: RYR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RYR2 were set to 30681346; 26573135; 22515980; 26656175; 30835254
Phenotypes for gene: RYR2 were set to Hypertrophic cardiomyopathy
Review for gene: RYR2 was set to AMBER
gene: RYR2 was marked as current diagnostic
Added comment: Limited evidence by ClinGen working group.

Via Clingen: 8 probands with HCM across 4 publications. A mouse model lends support to pathogenicity.

No additional reports in association with HCM found.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 MYPN Ain Roesley gene: MYPN was added
gene: MYPN was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: MYPN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYPN were set to 30681346; 20801532; 22286171
Phenotypes for gene: MYPN were set to Cardiomyopathy, hypertrophic, 22 (MIM# 615248)
Penetrance for gene: MYPN were set to unknown
Review for gene: MYPN was set to RED
Added comment: PMID: 30681346;
LIMITED by ClinGen working group.

Extract from ClinGen's curation:
Variants in this gene have been reported in at least 8 probands in 2 publications (PMIDs: 20801532, 22286171). This gene disease association is supported by expression studies, functional assays, and animal models. In summary, there is limited evidence to support this gene-disease relationship
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 TRIM63 Ain Roesley changed review comment from: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature; to: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- segregated in 3 families
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 TRIM63 Ain Roesley gene: TRIM63 was added
gene: TRIM63 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: TRIM63 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM63 were set to 30681346; 32451364
Phenotypes for gene: TRIM63 were set to Hypertrophic cardiomyopathy
Penetrance for gene: TRIM63 were set to unknown
Review for gene: TRIM63 was set to GREEN
Added comment: PMID: 30681346;
LIMITED by Clingen working group (last evaluated 2018)

PMID: 32451364
- 16 index cases with rare homozygous or compound heterozygous variants (15 HCM and one restrictive cardiomyopathy). None of these variants have homozygote counts in gnomAD.
- 1 index had another pathogenic truncating variant in MYBPC3
- 5 missense and 3 PTCs
- Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 MYOZ2 Paul De Fazio changed review comment from: Limited evidence by ClinGen working group.

Via ClinGen: Only one family (segregation in 5 members) has convincing association with disease. Other reports were either for variants that have population frequency suggesting benignity or in a proband where a variant in MYH7 was also found.

A review of the literature finds no other reports.; to: Limited evidence by ClinGen working group.

Via ClinGen: Only one family (segregation in 5 members) has convincing association with disease. Other reports were either for variants that have population frequency suggesting benignity or in a proband where a variant in MYH7 was also found. Studies in mice of two of these variants showed that they developed cardiac hypertrophy with preserved systolic function.

A review of the literature finds no other reports.
Hypertrophic cardiomyopathy_HCM v0.89 MYOZ2 Paul De Fazio edited their review of gene: MYOZ2: Changed publications: 17347475, 18591919, 28296734, 30681346, 22987565
Hypertrophic cardiomyopathy_HCM v0.89 MYOZ2 Paul De Fazio edited their review of gene: MYOZ2: Changed publications: 17347475, 18591919, 11114196, 30681346
Hypertrophic cardiomyopathy_HCM v0.89 MYOZ2 Paul De Fazio reviewed gene: MYOZ2: Rating: RED; Mode of pathogenicity: None; Publications: 17347475, 18591919, 11114196, 11114196, 30681346; Phenotypes: Cardiomyopathy, hypertrophic, 16 MIM#613838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 JPH2 Paul De Fazio reviewed gene: JPH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346, 17509612, 23973696, 26869393, 28393127, 30235249; Phenotypes: Cardiomyopathy, hypertrophic, MIM#613873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.89 KLF10 Naomi Baker gene: KLF10 was added
gene: KLF10 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: KLF10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLF10 were set to PMID: 22234868
Phenotypes for gene: KLF10 were set to HCM
Review for gene: KLF10 was set to RED
Added comment: Curated by ClinGen and rated as limited evidence.

Misssense mutations reported in six unrelated individuals patients (two males/four females), with family history of HCM only reported for one individual (PMID: 22234868). No further reports in the literature.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.89 TNNC1 Ain Roesley reviewed gene: TNNC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30681346, 11385718, 8572189, 21262074, 22815480, 26779504; Phenotypes: Cardiomyopathy, hypertrophic, 13 (MIM# 613243); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy_HCM v0.89 MYOM1 Zornitza Stark Classified gene: MYOM1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.89 MYOM1 Zornitza Stark Gene: myom1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Marked gene: TCAP as ready
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.88 TCAP Zornitza Stark Publications for gene: TCAP were set to
Hypertrophic cardiomyopathy_HCM v0.87 TCAP Zornitza Stark reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: 16352453, 15582318; Phenotypes: Cardiomyopathy, hypertrophic, 25, MIM# 607487; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.87 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Cardiomyopathy, hypertrophic, 25, MIM# 607487
Hypertrophic cardiomyopathy_HCM v0.86 TCAP Zornitza Stark Mode of inheritance for gene: TCAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.85 TCAP Zornitza Stark Classified gene: TCAP as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.85 TCAP Zornitza Stark Gene: tcap has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Marked gene: VCL as ready
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.84 VCL Zornitza Stark Phenotypes for gene: VCL were changed from to Cardiomyopathy, hypertrophic, 15, MIM# 613255
Hypertrophic cardiomyopathy_HCM v0.83 VCL Zornitza Stark Publications for gene: VCL were set to
Hypertrophic cardiomyopathy_HCM v0.82 VCL Zornitza Stark Mode of inheritance for gene: VCL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.81 VCL Zornitza Stark Classified gene: VCL as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.81 VCL Zornitza Stark Gene: vcl has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.80 VCL Zornitza Stark reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: 17097056; Phenotypes: Cardiomyopathy, hypertrophic, 15, MIM# 613255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Marked gene: NEXN as ready
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.80 NEXN Zornitza Stark Phenotypes for gene: NEXN were changed from to Cardiomyopathy, hypertrophic, 20, MIM# 613876
Hypertrophic cardiomyopathy_HCM v0.79 NEXN Zornitza Stark Publications for gene: NEXN were set to
Hypertrophic cardiomyopathy_HCM v0.78 NEXN Zornitza Stark Mode of inheritance for gene: NEXN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: 20970104; Phenotypes: Cardiomyopathy, hypertrophic, 20, MIM# 613876; Mode of inheritance: None
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark Classified gene: NEXN as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.77 NEXN Zornitza Stark Gene: nexn has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.76 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to 11733062; 24082139; 25825456; 20301725
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Marked gene: MYL3 as ready
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Gene: myl3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.75 MYL3 Zornitza Stark Phenotypes for gene: MYL3 were changed from to Cardiomyopathy, hypertrophic, 8, MIM# 608751
Hypertrophic cardiomyopathy_HCM v0.74 MYL3 Zornitza Stark Publications for gene: MYL3 were set to
Hypertrophic cardiomyopathy_HCM v0.73 MYL3 Zornitza Stark Mode of inheritance for gene: MYL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Marked gene: TNNI3 as ready
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Gene: tnni3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.72 TNNI3 Zornitza Stark Phenotypes for gene: TNNI3 were changed from to Cardiomyopathy, hypertrophic, 7, MIM# 613690
Hypertrophic cardiomyopathy_HCM v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to 30681346
Hypertrophic cardiomyopathy_HCM v0.71 TNNI3 Zornitza Stark Publications for gene: TNNI3 were set to
Hypertrophic cardiomyopathy_HCM v0.70 TNNI3 Zornitza Stark Mode of inheritance for gene: TNNI3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.69 TPM1 Zornitza Stark Publications for gene: TPM1 were set to 31270709
Hypertrophic cardiomyopathy_HCM v0.68 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to 20378854
Hypertrophic cardiomyopathy_HCM v0.67 MYBPC3 Ivan Macciocca reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.67 TPM1 Ivan Macciocca reviewed gene: TPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 TNNI3 Ivan Macciocca reviewed gene: TNNI3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.67 MYL3 Ivan Macciocca reviewed gene: MYL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYLK2 Ivan Macciocca reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: None; Publications: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 NEXN Ivan Macciocca reviewed gene: NEXN: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 VCL Ivan Macciocca reviewed gene: VCL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 TCAP Ivan Macciocca reviewed gene: TCAP: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYOM1 Ivan Macciocca reviewed gene: MYOM1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 MYH6 Ivan Macciocca reviewed gene: MYH6: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Marked gene: TNNT2 as ready
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Gene: tnnt2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.67 TNNT2 Zornitza Stark Publications for gene: TNNT2 were set to
Hypertrophic cardiomyopathy_HCM v0.66 TNNT2 Zornitza Stark Phenotypes for gene: TNNT2 were changed from to Cardiomyopathy, hypertrophic, 2, MIM# 115195
Hypertrophic cardiomyopathy_HCM v0.65 TNNT2 Zornitza Stark Mode of inheritance for gene: TNNT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Marked gene: MYL2 as ready
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Gene: myl2 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.64 MYL2 Zornitza Stark Publications for gene: MYL2 were set to
Hypertrophic cardiomyopathy_HCM v0.63 MYL2 Zornitza Stark Phenotypes for gene: MYL2 were changed from to Cardiomyopathy, hypertrophic, 10, MIM# 608758
Hypertrophic cardiomyopathy_HCM v0.62 MYL2 Zornitza Stark Mode of inheritance for gene: MYL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.61 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from to Cardiomyopathy, hypertrophic, 1, MIM# 192600
Hypertrophic cardiomyopathy_HCM v0.60 MYH7 Zornitza Stark Publications for gene: MYH7 were set to
Hypertrophic cardiomyopathy_HCM v0.59 MYH7 Zornitza Stark Mode of inheritance for gene: MYH7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.58 KLHL24 Zornitza Stark Marked gene: KLHL24 as ready
Hypertrophic cardiomyopathy_HCM v0.58 KLHL24 Zornitza Stark Gene: klhl24 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.58 FLNC Zornitza Stark Publications for gene: FLNC were set to 31924696; 28356264
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Marked gene: DES as ready
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.57 DES Zornitza Stark Phenotypes for gene: DES were changed from to Hypertrophic cardiomyopathy; Dilated cardiomyopathy; Myofibrillar myopathy; ARVC
Hypertrophic cardiomyopathy_HCM v0.56 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.55 DES Zornitza Stark Mode of inheritance for gene: DES was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.54 DES Zornitza Stark Classified gene: DES as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.54 DES Zornitza Stark Gene: des has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Marked gene: CSRP3 as ready
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Added comment: Comment when marking as ready: Sufficient number of families reported with good segregation data but agree caution needed in light of some of these variants being present at low frequency in the population.
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Gene: csrp3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.53 CSRP3 Zornitza Stark Phenotypes for gene: CSRP3 were changed from to Cardiomyopathy, hypertrophic, 12, MIM# 612124
Hypertrophic cardiomyopathy_HCM v0.52 CSRP3 Zornitza Stark Publications for gene: CSRP3 were set to
Hypertrophic cardiomyopathy_HCM v0.51 CSRP3 Zornitza Stark Mode of inheritance for gene: CSRP3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Marked gene: CAV3 as ready
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.50 CAV3 Zornitza Stark Phenotypes for gene: CAV3 were changed from to Cardiomyopathy, familial hypertrophic, MIM# 192600
Hypertrophic cardiomyopathy_HCM v0.49 CAV3 Zornitza Stark Publications for gene: CAV3 were set to
Hypertrophic cardiomyopathy_HCM v0.48 CAV3 Zornitza Stark Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.47 CAV3 Zornitza Stark Classified gene: CAV3 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.47 CAV3 Zornitza Stark Gene: cav3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Marked gene: CALR3 as ready
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Tag refuted tag was added to gene: CALR3.
Hypertrophic cardiomyopathy_HCM v0.46 CALR3 Zornitza Stark Phenotypes for gene: CALR3 were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.45 CALR3 Zornitza Stark Publications for gene: CALR3 were set to
Hypertrophic cardiomyopathy_HCM v0.44 CALR3 Zornitza Stark Mode of inheritance for gene: CALR3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.43 CALR3 Zornitza Stark Classified gene: CALR3 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.43 CALR3 Zornitza Stark Gene: calr3 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Marked gene: ANKRD1 as ready
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.42 ANKRD1 Zornitza Stark Phenotypes for gene: ANKRD1 were changed from to hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.41 ANKRD1 Zornitza Stark Publications for gene: ANKRD1 were set to
Hypertrophic cardiomyopathy_HCM v0.40 ANKRD1 Zornitza Stark Mode of inheritance for gene: ANKRD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.39 ANKRD1 Zornitza Stark Classified gene: ANKRD1 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.39 ANKRD1 Zornitza Stark Gene: ankrd1 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Marked gene: ALPK3 as ready
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Gene: alpk3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.38 ALPK3 Zornitza Stark Phenotypes for gene: ALPK3 were changed from to Cardiomyopathy, familial hypertrophic 27, MIM# 618052
Hypertrophic cardiomyopathy_HCM v0.37 ALPK3 Zornitza Stark Publications for gene: ALPK3 were set to
Hypertrophic cardiomyopathy_HCM v0.36 ALPK3 Zornitza Stark Mode of inheritance for gene: ALPK3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Marked gene: ACTN2 as ready
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.35 ACTN2 Zornitza Stark Phenotypes for gene: ACTN2 were changed from to Cardiomyopathy, hypertrophic, 23, with or without LVNC, MIM# 612158
Hypertrophic cardiomyopathy_HCM v0.34 ACTN2 Zornitza Stark Publications for gene: ACTN2 were set to
Hypertrophic cardiomyopathy_HCM v0.33 ACTN2 Zornitza Stark Mode of inheritance for gene: ACTN2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.32 ACTN2 Zornitza Stark Classified gene: ACTN2 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.32 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Marked gene: ACTC1 as ready
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Gene: actc1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.31 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.30 ACTC1 Zornitza Stark Phenotypes for gene: ACTC1 were changed from to Cardiomyopathy, hypertrophic, 11 612098
Hypertrophic cardiomyopathy_HCM v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.29 ACTC1 Zornitza Stark Mode of inheritance for gene: ACTC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 MYL2 Ivan Macciocca reviewed gene: MYL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 TNNT2 Ivan Macciocca reviewed gene: TNNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: HCM, LVNC, RCM, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 MYH7 Ivan Macciocca reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, LVNC, DCM; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 FLNC Ivan Macciocca reviewed gene: FLNC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30411535; Phenotypes: hypertrophic cardiomyopathy, distal myopathy, restrictive cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 DES Ivan Macciocca reviewed gene: DES: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: arrhythmogenic right ventricular cardiomyopathy, myofibrillar myopathy 1, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 CSRP3 Ivan Macciocca changed review comment from: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.; to: Assessed as MODERATE by ClinGen HCM working group PMID: 30681346
Associated with HCM in 4 families reported by a German group with some functional evidence and including 2 large multi-generational families with 6 and 8 affected relatives segregating the variants.
3 of the 4 variants reported in these families have a low frequency (up to 4 alleles) in Gnomad.
Assess variants in this gene with caution due to the limited number of families currently reported with pathogenic/likely[pathogenic variants in this gene.
Hypertrophic cardiomyopathy_HCM v0.28 CSRP3 Ivan Macciocca reviewed gene: CSRP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18505755, 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 CAV3 Ivan Macciocca reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 14672715,27483260,12138167; Phenotypes: hypertrophic cardiomyopathy, long QT syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 C1QBP Ivan Macciocca reviewed gene: C1QBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:28942965; Phenotypes: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 33, hypertrophic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 ANKRD1 Ivan Macciocca reviewed gene: ANKRD1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 ALPK3 Ivan Macciocca reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26846950, 27106955, 32480058; Phenotypes: hypertrophic cardiomyopathy, dilated cardiomyopathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.28 ACTN2 Ivan Macciocca reviewed gene: ACTN2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 30681346; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 ACTC1 Ivan Macciocca reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hypertrophic cardiomyopathy, left ventricular non compaction, dilated cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.28 MYLK2 Zornitza Stark Marked gene: MYLK2 as ready
Hypertrophic cardiomyopathy_HCM v0.28 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.28 MYLK2 Zornitza Stark Phenotypes for gene: MYLK2 were changed from to Cardiomyopathy, hypertrophic, 1, digenic, 192600
Hypertrophic cardiomyopathy_HCM v0.27 MYLK2 Zornitza Stark Publications for gene: MYLK2 were set to
Hypertrophic cardiomyopathy_HCM v0.26 MYLK2 Zornitza Stark Mode of pathogenicity for gene: MYLK2 was changed from to Other
Hypertrophic cardiomyopathy_HCM v0.25 MYLK2 Zornitza Stark Mode of inheritance for gene: MYLK2 was changed from Unknown to Other
Hypertrophic cardiomyopathy_HCM v0.24 MYLK2 Zornitza Stark Classified gene: MYLK2 as Red List (low evidence)
Hypertrophic cardiomyopathy_HCM v0.24 MYLK2 Zornitza Stark Gene: mylk2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy_HCM v0.23 MYLK2 Kristin Rigbye reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: Other; Publications: 11733062, 24082139, 25825456, 20301725; Phenotypes: Cardiomyopathy, hypertrophic, 1, digenic, 192600; Mode of inheritance: Other
Hypertrophic cardiomyopathy_HCM v0.23 KLHL24 Zornitza Stark Mode of inheritance for gene: KLHL24 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.22 KLHL24 Zornitza Stark Phenotypes for gene: KLHL24 were changed from Epidermolysis bullosa simplex, generalized, with scarring and hair loss, 617294; Hypertrophic cardiomyopathy to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.22 KLHL24 Zornitza Stark Mode of inheritance for gene: KLHL24 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.21 KLHL24 Zornitza Stark Classified gene: KLHL24 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.21 KLHL24 Zornitza Stark Gene: klhl24 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.20 KLHL24 Kristin Rigbye gene: KLHL24 was added
gene: KLHL24 was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: KLHL24 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KLHL24 were set to 27798626; 27889062; 30715372
Phenotypes for gene: KLHL24 were set to Epidermolysis bullosa simplex, generalized, with scarring and hair loss, 617294; Hypertrophic cardiomyopathy
Review for gene: KLHL24 was set to GREEN
Added comment: Heterozygous variants in the start codon, resulting in the use of alternate downstream methionine at residue 29, have previously been reported in multiple patients with AD EBS. These variants have been shown to cause a gain of function, resulting in enhanced protein stability and higher abundance (OMIM).

Recent report of recessive KLHL24 variants in 2 unrelated consanguineous families (total of 7 sequenced affected individuals) with HCM (1 nonsense, 1 missense). A knockdown model of klhl24a in zebrafish recapitulated the cardiac phenotype, supporting loss of function as the mechanism in AR HCM (PMID: 30715372).
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.20 NEBL Zornitza Stark Marked gene: NEBL as ready
Hypertrophic cardiomyopathy_HCM v0.20 NEBL Zornitza Stark Gene: nebl has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.20 NEBL Zornitza Stark Classified gene: NEBL as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.20 NEBL Zornitza Stark Gene: nebl has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.19 NEBL Zornitza Stark gene: NEBL was added
gene: NEBL was added to Hypertrophic cardiomyopathy_HCM. Sources: Literature
Mode of inheritance for gene: NEBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEBL were set to 27186169
Phenotypes for gene: NEBL were set to Hypertrophic cardiomyopathy; dilated cardiomyopathy
Review for gene: NEBL was set to GREEN
Added comment: 7 individuals from 6 unrelated families described with missense variants in this gene; some with HOCM, some with DCM.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.18 CALR3 Kristin Rigbye reviewed gene: CALR3: Rating: RED; Mode of pathogenicity: Other; Publications: 29988065; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy_HCM v0.18 TPM1 Zornitza Stark Marked gene: TPM1 as ready
Hypertrophic cardiomyopathy_HCM v0.18 TPM1 Zornitza Stark Gene: tpm1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.18 TPM1 Zornitza Stark Phenotypes for gene: TPM1 were changed from to Cardiomyopathy, dilated, 1Y, 611878; Cardiomyopathy, hypertrophic, 3, 115196; Left ventricular noncompaction 9, 611878
Hypertrophic cardiomyopathy_HCM v0.17 TPM1 Zornitza Stark Publications for gene: TPM1 were set to
Hypertrophic cardiomyopathy_HCM v0.16 TPM1 Zornitza Stark Mode of pathogenicity for gene: TPM1 was changed from to Other
Hypertrophic cardiomyopathy_HCM v0.15 TPM1 Zornitza Stark Mode of inheritance for gene: TPM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.14 MYBPC3 Zornitza Stark Marked gene: MYBPC3 as ready
Hypertrophic cardiomyopathy_HCM v0.14 MYBPC3 Zornitza Stark Gene: mybpc3 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.14 MYBPC3 Zornitza Stark Phenotypes for gene: MYBPC3 were changed from to Cardiomyopathy, dilated, 1MM, 615396; Cardiomyopathy, hypertrophic, 4, 115197; Left ventricular noncompaction 10, 615396
Hypertrophic cardiomyopathy_HCM v0.13 MYBPC3 Zornitza Stark Publications for gene: MYBPC3 were set to
Hypertrophic cardiomyopathy_HCM v0.12 MYBPC3 Zornitza Stark Mode of inheritance for gene: MYBPC3 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypertrophic cardiomyopathy_HCM v0.11 TPM1 Kristin Rigbye Deleted their comment
Hypertrophic cardiomyopathy_HCM v0.11 TPM1 Kristin Rigbye edited their review of gene: TPM1: Added comment: Well known gene-disease association.
Mechanism not established, but likely gain of function; it's possible that HCM variants are GoF, whilst DCM variants are LoF (PMID: 31270709).; Changed phenotypes: Cardiomyopathy, dilated, 1Y, 611878, Cardiomyopathy, hypertrophic, 3, 115196, Left ventricular noncompaction 9, 611878
Hypertrophic cardiomyopathy_HCM v0.11 MYBPC3 Kristin Rigbye reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20378854; Phenotypes: Cardiomyopathy, dilated, 1MM, 615396, Cardiomyopathy, hypertrophic, 4, 115197, Left ventricular noncompaction 10, 615396; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.11 MYBPC3 Kristin Rigbye Deleted their review
Hypertrophic cardiomyopathy_HCM v0.11 MYBPC3 Kristin Rigbye changed review comment from: Well known gene-disease association; to: Well known gene-disease association
Hypertrophic cardiomyopathy_HCM v0.11 TPM1 Kristin Rigbye reviewed gene: TPM1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31270709; Phenotypes: Cardiomyopathy, dilated, 1Y, Cardiomyopathy, hypertrophic, 3, Left ventricular noncompaction 9; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.11 MYBPC3 Kristin Rigbye reviewed gene: MYBPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20378854; Phenotypes: Cardiomyopathy, dilated, 1MM, Cardiomyopathy, hypertrophic, 4, Left ventricular noncompaction 10; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Hypertrophic cardiomyopathy_HCM v0.11 FLNC Zornitza Stark Marked gene: FLNC as ready
Hypertrophic cardiomyopathy_HCM v0.11 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.11 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.11 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.10 FLNC Zornitza Stark gene: FLNC was added
gene: FLNC was added to Hypertrophic cardiomyopathy_HCM. Sources: Expert Review
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLNC were set to 31924696; 28356264
Phenotypes for gene: FLNC were set to Cardiomyopathy, familial hypertrophic, 26
Review for gene: FLNC was set to GREEN
Added comment: Multiple affected individuals with cardiomyopathy, including HOCM reported.
Sources: Expert Review
Hypertrophic cardiomyopathy_HCM v0.9 MYOM1 Zornitza Stark Marked gene: MYOM1 as ready
Hypertrophic cardiomyopathy_HCM v0.9 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.9 MYOM1 Zornitza Stark Phenotypes for gene: MYOM1 were changed from to Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy_HCM v0.8 MYOM1 Zornitza Stark Publications for gene: MYOM1 were set to
Hypertrophic cardiomyopathy_HCM v0.7 MYOM1 Zornitza Stark Mode of inheritance for gene: MYOM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.6 MYOM1 Zornitza Stark Classified gene: MYOM1 as Amber List (moderate evidence)
Hypertrophic cardiomyopathy_HCM v0.6 MYOM1 Zornitza Stark Gene: myom1 has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy_HCM v0.5 MYOM1 Zornitza Stark reviewed gene: MYOM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27600940, 26656175, 21256114; Phenotypes: Hypertrophic cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy_HCM v0.5 Zornitza Stark Panel name changed from Hypertrophic cardiomyopathy_VCGS to Hypertrophic cardiomyopathy_HCM
Panel types changed to Victorian Clinical Genetics Services
Hypertrophic cardiomyopathy_HCM v0.4 UQCRFS1 Zornitza Stark Marked gene: UQCRFS1 as ready
Hypertrophic cardiomyopathy_HCM v0.4 UQCRFS1 Zornitza Stark Gene: uqcrfs1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.4 UQCRFS1 Zornitza Stark Classified gene: UQCRFS1 as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.4 UQCRFS1 Zornitza Stark Gene: uqcrfs1 has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.3 UQCRFS1 Zornitza Stark gene: UQCRFS1 was added
gene: UQCRFS1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Literature
Mode of inheritance for gene: UQCRFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCRFS1 were set to 31883641
Phenotypes for gene: UQCRFS1 were set to Mitochondrial Complex III deficiency; lactic acidosis; fetal bradycardia; hypertrophic cardiomyopathy; alopecia totalis
Review for gene: UQCRFS1 was set to GREEN
Added comment: Two unrelated families reported plus functional evidence.
Sources: Literature
Hypertrophic cardiomyopathy_HCM v0.2 C1QBP Zornitza Stark Marked gene: C1QBP as ready
Hypertrophic cardiomyopathy_HCM v0.2 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.2 C1QBP Zornitza Stark Classified gene: C1QBP as Green List (high evidence)
Hypertrophic cardiomyopathy_HCM v0.2 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Hypertrophic cardiomyopathy_HCM v0.1 C1QBP Zornitza Stark gene: C1QBP was added
gene: C1QBP was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert list
Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QBP were set to 28942965
Phenotypes for gene: C1QBP were set to Combined oxidative phosphorylation deficiency 33, MIM#617713
Review for gene: C1QBP was set to GREEN
Added comment: Four unrelated families reported; hypertrophic cardiomyopathy is a feature of the condition.
Sources: Expert list
Hypertrophic cardiomyopathy_HCM v0.0 VCL Zornitza Stark gene: VCL was added
gene: VCL was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: VCL was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TTR Zornitza Stark gene: TTR was added
gene: TTR was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TTR was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TTN Zornitza Stark gene: TTN was added
gene: TTN was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TTN was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TPM1 Zornitza Stark gene: TPM1 was added
gene: TPM1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TPM1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TNNT2 Zornitza Stark gene: TNNT2 was added
gene: TNNT2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNNT2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TNNI3 Zornitza Stark gene: TNNI3 was added
gene: TNNI3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNNI3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TNNC1 Zornitza Stark gene: TNNC1 was added
gene: TNNC1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TNNC1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 TCAP Zornitza Stark gene: TCAP was added
gene: TCAP was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TCAP was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 SLC25A4 Zornitza Stark gene: SLC25A4 was added
gene: SLC25A4 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A4 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 RAF1 Zornitza Stark gene: RAF1 was added
gene: RAF1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAF1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 PTPN11 Zornitza Stark gene: PTPN11 was added
gene: PTPN11 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PTPN11 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 PRKAG2 Zornitza Stark gene: PRKAG2 was added
gene: PRKAG2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PRKAG2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 PLN Zornitza Stark gene: PLN was added
gene: PLN was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PLN was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 NEXN Zornitza Stark gene: NEXN was added
gene: NEXN was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NEXN was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYOZ2 Zornitza Stark gene: MYOZ2 was added
gene: MYOZ2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYOZ2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYOM1 Zornitza Stark gene: MYOM1 was added
gene: MYOM1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYOM1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYLK2 Zornitza Stark gene: MYLK2 was added
gene: MYLK2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYLK2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYL3 Zornitza Stark gene: MYL3 was added
gene: MYL3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYL3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYL2 Zornitza Stark gene: MYL2 was added
gene: MYL2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYL2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYH7 Zornitza Stark gene: MYH7 was added
gene: MYH7 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYH7 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYH6 Zornitza Stark gene: MYH6 was added
gene: MYH6 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYH6 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 MYBPC3 Zornitza Stark gene: MYBPC3 was added
gene: MYBPC3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MYBPC3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 LAMP2 Zornitza Stark gene: LAMP2 was added
gene: LAMP2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAMP2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 JPH2 Zornitza Stark gene: JPH2 was added
gene: JPH2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: JPH2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 GLA Zornitza Stark gene: GLA was added
gene: GLA was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GLA was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 GAA Zornitza Stark gene: GAA was added
gene: GAA was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GAA was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 FXN Zornitza Stark gene: FXN was added
gene: FXN was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FXN was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 DES Zornitza Stark gene: DES was added
gene: DES was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DES was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 CSRP3 Zornitza Stark gene: CSRP3 was added
gene: CSRP3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CSRP3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 CAV3 Zornitza Stark gene: CAV3 was added
gene: CAV3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CAV3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 CALR3 Zornitza Stark gene: CALR3 was added
gene: CALR3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CALR3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 ANKRD1 Zornitza Stark gene: ANKRD1 was added
gene: ANKRD1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ANKRD1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 ALPK3 Zornitza Stark gene: ALPK3 was added
gene: ALPK3 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ALPK3 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 ACTN2 Zornitza Stark gene: ACTN2 was added
gene: ACTN2 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ACTN2 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 ACTC1 Zornitza Stark gene: ACTC1 was added
gene: ACTC1 was added to Hypertrophic cardiomyopathy_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ACTC1 was set to Unknown
Hypertrophic cardiomyopathy_HCM v0.0 Zornitza Stark Added panel Hypertrophic cardiomyopathy_VCGS