ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2182G>T (p.Glu728Ter) (rs397515954)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000768471 SCV000059121 pathogenic Hypertrophic cardiomyopathy 2018-06-04 criteria provided, single submitter clinical testing The p.Glu728X variant in MYBPC3 has been identified in 3 individuals with HCM an d segregated with disease in 3 affected relatives (LMM data). It was absent from large population databases. This nonsense variant leads to a premature terminat ion codon at position 728, which is predicted to lead to a truncated or absent p rotein. Heterozygous loss of function of the MYBPC3 gene is an established disea se mechanism in HCM. In summary, this variant meets our criteria to be classifie d as pathogenic based on predicted impact on the protein, absence from controls, case observations, and segregation in affected family members. ACMG/AMP Criteri a applied: PVS1, PM2, PP1, PS4_Supporting.
GeneDx RCV000158141 SCV000208076 pathogenic not provided 2014-06-10 criteria provided, single submitter clinical testing p.Glu728Stop (GAG>TAG): c.2182 G>T in exon 23 of the MYBPC3 gene (NM_000256.3)The E728X mutation in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. E728X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the MYBPC3 gene have been reported in association with HCM. In summary, E728X in the MYBPC3 gene is interpreted as a disease-causing mutation. Mutations in the MYBPC3 gene have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy, and have been reported less frequently in patients with autosomal dominant familial dilated cardiomyopathy (CirinoAet al., 2011; Hershberger R et al., 2009). The variant is found in HCM panel(s).
Center for Human Genetics,University of Leuven RCV000768471 SCV000886757 pathogenic Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing

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