ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3414dup (p.Val1139fs) (rs863225114)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000201466 SCV000256186 likely pathogenic Familial hypertrophic cardiomyopathy 4 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000201466 SCV001164416 likely pathogenic Familial hypertrophic cardiomyopathy 4 2018-12-03 criteria provided, single submitter research The heterozygous p.Val1139ArgfsTer10 variant in MYBPC3 was identified by our study in one individual with hypertrophic cardiomyopathy. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 1139 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Greater than 10% of pathogenic variants reported in association with hypertrophic cardiomyopathy in ClinVar are loss of function variants, including at least three pathogenic loss of function variants across multiple exons. Heterozygous loss of function of the MYBPC3 gene is an established disease mechanism for hypertrophic cardiomyopathy. In summary, although additional studies are required to establish its clinical significance, the p.Val1139ArgfsTer10 variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015).

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