Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522924 | SCV000621757 | uncertain significance | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the MYBPC3 gene. The V783M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). However, the V783M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to valine (V) are tolerated across species. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Ambry Genetics | RCV002431492 | SCV002731894 | uncertain significance | Cardiovascular phenotype | 2022-06-09 | criteria provided, single submitter | clinical testing | The p.V783M variant (also known as c.2347G>A), located in coding exon 24 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2347. The valine at codon 783 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003748245 | SCV004532445 | uncertain significance | Hypertrophic cardiomyopathy | 2023-01-17 | criteria provided, single submitter | clinical testing | 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"). 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. ClinVar contains an entry for this variant (Variation ID: 452909). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 783 of the MYBPC3 protein (p.Val783Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. |