Activity

Filter

Cancel
Date Panel Item Activity
17 actions
Hypertrophic cardiomyopathy v5.12 SVIL Ida Ertmanska changed review comment from: Comment on list classification: The main piece of evidence for this gene-disease association is a GWAS study, with very limited co-segregation evidence (PMID: 39966646). There are no other cases reported with Hypertrophic cardiomyopathy and heterozygous variants in SVIL. Individuals homozygous for nonsense variants in SVIL have been reported, but the myopathy presentation includes very mild to no cardiac involvement (PMID: 32779703). Based on available evidence, this gene should be rated Amber for Hypertrophic cardiomyopathy, until more evidence emerges.; to: Comment on list classification: The main piece of evidence for this gene-disease association is a GWAS study, with no clinical details and limited co-segregation evidence (PMID: 39966646). There are no other cases reported with Hypertrophic cardiomyopathy and heterozygous variants in SVIL. Individuals homozygous for nonsense variants in SVIL have been reported, but the myopathy presentation includes very mild to no cardiac involvement (PMID: 32779703). Based on available evidence, this gene should be rated Amber for Hypertrophic cardiomyopathy, until more evidence emerges.
Hypertrophic cardiomyopathy v5.12 SVIL Ida Ertmanska edited their review of gene: SVIL: Added comment: Comment on list classification: The main piece of evidence for this gene-disease association is a GWAS study, with very limited co-segregation evidence (PMID: 39966646). There are no other cases reported with Hypertrophic cardiomyopathy and heterozygous variants in SVIL. Individuals homozygous for nonsense variants in SVIL have been reported, but the myopathy presentation includes very mild to no cardiac involvement (PMID: 32779703). Based on available evidence, this gene should be rated Amber for Hypertrophic cardiomyopathy, until more evidence emerges.; Changed rating: AMBER
Hypertrophic cardiomyopathy v5.12 MT-ND5 Achchuthan Shanmugasundram changed review comment from: PMID:14520659 - Three unrelated patients with Leigh's syndrome were identified with m.13513G>A variant in MT-ND5 gene, of which one patient was reported with hypertrophic cardiomyopathy (HCM) among other clinical presentations.

PMID:22759514 - A 3-generation family of Han Chinese descent was reported with maternally inherited isolated HCM. They were identified with a homoplasmic m.12338T>C variant in MT-ND5 gene, leading to the replacement of initiation methionine residue to Threonine, resulting in shortening of the ND5 polypeptide by 2 amino acids.

PMID:23847141 - This study analysed the while mitochondrial DNA sequences of a cohort of 743 patients suspected of manifesting a mitochondrial disease. Nine patients were detected with a variant in MT-ND5 gene, and they presented with different combinations of phenotypes. One of four patients with m.13513G>A variants had HCM as one of the clinical features.

PMID:30587702 - A 21-year-old proband presented with biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance. Skeletal muscle biopsy showed features consistent with mitochondrial myopathy. The family was identified with c.1315A>G (p.Thr439Ala) variant in MT-ND5 gene.; to: PMID:14520659 - Three unrelated patients with Leigh's syndrome were identified with m.13513G>A variant in MT-ND5 gene, of which one patient was reported with hypertrophic cardiomyopathy (HCM) among other clinical presentations.

PMID:22759514 - A 3-generation family of Han Chinese descent was reported with maternally inherited isolated HCM. They were identified with a homoplasmic m.12338T>C variant in MT-ND5 gene, leading to the replacement of initiation methionine residue to Threonine, resulting in shortening of the ND5 polypeptide by 2 amino acids.

PMID:23847141 - This study analysed the mitochondrial DNA sequences of a cohort of 743 patients suspected of manifesting a mitochondrial disease. Nine patients were detected with a variant in MT-ND5 gene, and they presented with different combinations of phenotypes. One of four patients with m.13513G>A variants had HCM as one of the clinical features.

PMID:30587702 - A 21-year-old proband presented with biventricular hypertrophy, hyperlactacidemia, pulmonary hypertension, and decreased exercise tolerance. Skeletal muscle biopsy showed features consistent with mitochondrial myopathy. The family was identified with c.1315A>G (p.Thr439Ala) variant in MT-ND5 gene.
Hypertrophic cardiomyopathy v4.7 SVIL Dmitrijs Rots gene: SVIL was added
gene: SVIL was added to Hypertrophic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: SVIL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SVIL were set to PMID: 36778260
Phenotypes for gene: SVIL were set to HCM
Review for gene: SVIL was set to AMBER
Added comment: In the novel paper described:"the excess burden is even greater at 15.3-fold (95% CI: 5.7-41.3; P:7x10−7) when restricting the analysis to high confidence LoF variants affecting the predominant SVIL transcript in LV (ENST00000375400) (Supplementary Table 6b). In one family, the SVIL LoF variant (p.(Gln255*)) was carried by two cousins with HCM (parents deceased), providing some evidence of co-segregation. Taken together, these data support SVIL as a novel HCM disease gene."
Strong statistical evidence + one family segregating.
Sources: Literature
Hypertrophic cardiomyopathy v4.7 ALPK3 Dmitrijs Rots commented on gene: ALPK3: As described by Luis Lopes, should be BOTH monoallelic and biallelic on this panel.
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
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
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
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