Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158452 | SCV000208387 | pathogenic | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 17394878, 24111713, 21896538, 28971120, 20624503, 28640247) |
Laboratory for Molecular Medicine, |
RCV000219427 | SCV000271406 | pathogenic | Hypertrophic cardiomyopathy | 2015-07-01 | criteria provided, single submitter | clinical testing | The p.Tyr79X variant in MYBPC3 has been reported in 1 Caucasian individual with HCM, segregated with disease in 3 affected relatives (including 1 obligate carri er), and was absent from 200 ethnically matched controls (Garcia-Pavia 2007, Gar cia-Pavia 2011). It has also been detected by another clinical testing laborato ry and is noted in the ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/var iation/181132). Data from large population studies is insufficient to assess the frequency of this variant. This nonsense variant leads to a premature terminati on codon at position 79, which is predicted to lead to a truncated or absent pro tein. Heterozygous loss of function of the MYBPC3 gene is an established disease mechanism in individuals with HCM. In summary, this variant meets our criteria to be classified as pathogenic for HCM in an autosomal dominant manner (http://w ww.partners.org/personalizedmedicine/LMM) based on the predicted impact of the v ariant. |
3billion | RCV002283460 | SCV002573041 | pathogenic | Hypertrophic cardiomyopathy 4 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000181132 / PMID: 17394878). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |