Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497659 | SCV000589440 | uncertain significance | not provided | 2018-03-01 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSC2 gene. The V361M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 6/30772 (0.02%) alleles from individuals of South Asian ancestry in large population cohorts (Lek et al., 2016). The V361M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. |
Ambry Genetics | RCV000622048 | SCV000735949 | likely benign | Cardiovascular phenotype | 2022-03-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Color Diagnostics, |
RCV000772025 | SCV000904981 | likely benign | Cardiomyopathy | 2020-04-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001233237 | SCV001405820 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 361 of the DSC2 protein (p.Val361Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs751810874, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 431881). 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: "Tolerated"; 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. |
All of Us Research Program, |
RCV004003495 | SCV004816178 | likely benign | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-10-06 | criteria provided, single submitter | clinical testing |