Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522426 | SCV000617135 | uncertain significance | not provided | 2017-09-15 | criteria provided, single submitter | clinical testing | The V138M variant of uncertain significance in the MYH7 gene has not been published as pathogenic or been reported as benign to our knowledge. V138M is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the V138M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, it occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Multiple missense variants in nearby residues (T135I, V139L, Y142H, R143W, R143G, R143Q) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), yet the pathogenicity of each of these variants has not been definitively determined. |
Invitae | RCV001038787 | SCV001202281 | uncertain significance | Hypertrophic cardiomyopathy | 2019-11-26 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 449244). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 138 of the MYH7 protein (p.Val138Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. |