Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151063 | SCV000198801 | uncertain significance | not specified | 2014-08-07 | criteria provided, single submitter | clinical testing | The Met1229Val variant in MYBPC3 has not been previously reported in any other f amilies with cardiomyopathy or in large population studies. Computational predic tion tools and conservation analysis suggest that the Met1229Val variant may not impact the protein, though this information is not predictive enough to rule ou t pathogenicity. In summary, the clinical significance of the Met1229Val variant is uncertain. |
Invitae | RCV001366308 | SCV001562609 | uncertain significance | Hypertrophic cardiomyopathy | 2020-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 1229 of the MYBPC3 protein (p.Met1229Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 164028). |