ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1283C>T (p.Ala428Val) (rs727503266)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000151291 SCV000199225 likely pathogenic Hypertrophic cardiomyopathy 2018-11-28 criteria provided, single submitter clinical testing The p.Ala428Val variant in MYH7 has been identified in 4 individuals with hypert rophic cardiomyopathy (HCM; Richard 2003, Van Driest 2004, Walsh 2017, LMM data) and is absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. This varia nt is located in the head domain of the MYH7 protein, where studies have shown t hat variants in this region have an increased probability for causing disease (W alsh 2017). In summary, although additional studies are required to fully establ ish its clinical significance, this variant meets criteria to be classified as l ikely pathogenic for autosomal dominant HCM based upon its presence in multiple affected individuals, absence from the general population, presence in a functio nal domain and computational evidence. ACMG/AMP Criteria applied: PS4_Supporting , PM1, PM2, PP3.

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