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| Hypertrophic cardiomyopathy v2.43 | RPS6KB1 |
Arina Puzriakova gene: RPS6KB1 was added gene: RPS6KB1 was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Literature Q4_22_promote_green tags were added to gene: RPS6KB1. Mode of inheritance for gene: RPS6KB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RPS6KB1 were set to 34916228 Phenotypes for gene: RPS6KB1 were set to Hypertrophic cardiomyopathy Review for gene: RPS6KB1 was set to GREEN Added comment: Jain et al. 2022 (PMID: 34916228) reported on two unrelated HCM families with the same heterozygous missense RPS6KB1 variant (p.G47W), and subsequently three further unrelated probands with HCM harbouring distinct heterozygous variants (p.Q49K, p.Y62H, respectively). Variants segregated with disease, were predicted pathogenic by silico analyses and were ultrarare or absent in population databases. Functional studies in the HL-1 (mouse cardiomyocytes) cells showed that the patient-specific RPS6KB1 mutant significantly increased cell size and activated rpS6 and ERK1/2 signalling cascades. The relationship between RPS6KB1 and cardiac hypertrophy has also been explored in feline and mice models (PMID: 15226426; 17976640) Sources: Literature |
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| Hypertrophic cardiomyopathy v2.7 | ATAD3A |
Ivone Leong gene: ATAD3A was added gene: ATAD3A was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Literature watchlist tags were added to gene: ATAD3A. Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ATAD3A were set to 27640307; 28652416; 28158749; 31727539 Phenotypes for gene: ATAD3A were set to Harel-Yoon syndrome, 617183 Review for gene: ATAD3A was set to AMBER Added comment: Added new gene as Amber based on the available literature. As not every patient with a monoallelic/biallelic variant in this gene presented with HCM, this gene has been rated Amber until further evidence is available. PMID: 27640307 describes 5 patients from 5 unrelated families with the same de novo variant (c.1582 C>T, R528W). 3/5 patients have optic atrophy and 2/5 have HCM. The authors have suggested that R528W exerts a dominant negative effect. Three patients from 2 additional families have biallelic variants (1 compound heterozygous and 1 biallelic deletion of ATAD3B and ATAD3A). These 3 patients did not have optic atrophy nor HCM, but had congenital cataracts. PMID: 28158749 describes a family with monoallelic variant (c.1064 G>A, G355D) where affected mother and son do not have optic atrophy nor HCM but have hereditary spastic paraplegia. PMID: 31727539 describes a consanguineous family with 4 affected individuals with biallelic variant (c.1217T>G, L406R). 3/4 had congenital cataracts and 4/4 had HCM. No one had optic atrophy. Sources: Literature |
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| Hypertrophic cardiomyopathy v1.53 | DES | Rebecca Whittington commented on gene: DES: Myopathy, myofibrillar, 1 (601419 ) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | LMNA | Rebecca Whittington commented on gene: LMNA: 1 report on HGMD associated with HCM, other cardiomyopathy phenotypes described | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | GUSB | Rebecca Whittington commented on gene: GUSB: Patients with cardiac arrest and HCM described on OMIM, but not a key feature or presenting feature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | CACNA1C | Rebecca Whittington commented on gene: CACNA1C: HGMD - 1 variant described with HCM Pubmed: 24183960 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | MYPN | Rebecca Whittington commented on gene: MYPN: Very rare assoc with cardiomyopathy. 23 DM variants on HGMD ranging from missense to truncation. Majority associated with some type of cardiomyopathy. Duboscq-Bidot L et al (2008). Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy. Cardiovasc Res. 77: 118-125. Purevjav (2012) Hum Mol Genet 21: 2039 PubMed: 22286171. Chen (2017) J Transl Med 15: 78 PubMed: 28427417. MYPN mutations cause either a cardiac (AD) or a congenital skeletal muscle disorder (AR) through different modes of inheritance pUBMED 28220527. Functional evidence only - 28082330, 28369730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | JPH2 | Rebecca Whittington commented on gene: JPH2: Weak evidence for primary role in pathogenicity: 28082330. Insufficient evidence, no supporting segregation, despite functional assays. PMID: 28393127 - a novel variant identified in a proband with significant basal septal hypertrophy. Neither parents were genotyped. his mutation was absent in 159,358 reference alleles. Variants in in MYH7, MYBPC3, MYL2, MYL3, TTNT2, TTNI3, TNNC1, TPM1, ACTC, PRKAG2, GLA, and LAMP2 genes, were excluded in this patient. Mice with this variant exhibit similar basal hypertrophy using a newly developed echo imaging plane, and this was confirmed using cardiac MRI. Histological analysis demonstrated cardiomyocyte hypertrophy and disarray consistent with HCM. 3 additional missense variants reported in 3 cases in PMID: 17509612 (2007), however another missense variant Gly550Ser in this gene has been reclassified as unknown pathogenic significance, due to presence in allele frequency databases. HGMD: 8 DM variants - 3 DCM rest HCM. Functional studies shown an effect in JPH2 but no variants with evidence of segregation. 10.1093/eurheartj/ehw603 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.52 | DES | Rebecca Whittington commented on gene: DES: 3 DM variants associated with HCM on HGMD. Pubmed: 29167554, 29907873 with mixed phenotypes. Functional characterisation in 1 variant 21262226, 17221859 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.51 | DES | Rebecca Whittington reviewed gene: DES: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.45 | DES |
Ellen McDonagh Source South West GLH was added to DES. Mode of inheritance for gene DES was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Hypertrophic cardiomyopathy v1.40 | LZTR1 |
Anna de Burca gene: LZTR1 was added gene: LZTR1 was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Literature Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: LZTR1 were set to 30368668; 30732632 Phenotypes for gene: LZTR1 were set to RASopathy-associated cardiomyopathy Review for gene: LZTR1 was set to GREEN Added comment: PMID:30368668 describes the clinical phenotype of 7 unrelated patients with Noonan or Noonan-like syndrome associated with monoallelic or biallelic variants in LZTR1. Five of the patients (one with biallelic variants and four with monoallelic variants) had hypertrophic cardiomyopathy. PMID:30732632 describes the phenotype in 46 unrelated children with RASopathy derived from a cohort of 168 paediatric HCM patients. One of the 46 children with RASopathy had compound heterozygous missense variants in LZTR1, although it is unclear whether this gene was tested in all participants, as it was not included in the exome-based 'expanded cardiomyopathy' panel applied. Given the phenotypic variability of Noonan syndrome, it seems plausible that mild cases could present with apparently isolated hypertrophic cardiomyopathy. Sources: Literature |
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