ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2541C>G (p.Tyr847Ter) (rs397515974)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000158167 SCV000927926 pathogenic not provided 2018-09-11 criteria provided, single submitter clinical testing
GeneDx RCV000158167 SCV000208102 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing The Y847X variant in the MYBPC3 gene has been reported in several individuals with HCM in published literature and observed in multiple individuals with HCM referred for genetic testing at GeneDx (Van Driest et al., 2004; Berge et al., 2014; Kapplinger et al., 2014; Viswanathan et al., 2017; Zhao et al., 2017). This variant also segregated with disease in one affected relative from one family at GeneDx. Y847X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the MYBPC3 gene, including the same Y847X variant due to a different nucleotide change (c.2451 C>A), have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014). Furthermore, the Y847X variant is not observed in large population cohorts (Lek et al., 2016).
Invitae RCV000629027 SCV000749937 pathogenic Hypertrophic cardiomyopathy 2018-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr847*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with hypertrophic cardiomyopathy (PMID: 15519027, 24111713, 28193612, 28450932). ClinVar contains an entry for this variant (Variation ID: 42636). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: PMID: 19574547). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000629027 SCV000059154 pathogenic Hypertrophic cardiomyopathy 2014-02-24 criteria provided, single submitter clinical testing
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000035504 SCV000256185 likely pathogenic Familial hypertrophic cardiomyopathy 4 criteria provided, single submitter clinical testing

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