Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002949131 | SCV003278635 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 899 of the DSC2 protein (p.Met899Leu). This variant is present in population databases (rs754521188, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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. 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. |
| Ambry Genetics | RCV004068089 | SCV005028837 | likely benign | Cardiovascular phenotype | 2023-10-08 | 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. |