Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001965634 | SCV002244837 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 825 of the DSC2 protein (p.Glu825Asp). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1460984). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs776401728, gnomAD 0.01%). |
Ambry Genetics | RCV004044419 | SCV003755329 | likely benign | Cardiovascular phenotype | 2022-08-17 | 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. |
Mayo Clinic Laboratories, |
RCV003481222 | SCV004224470 | uncertain significance | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | BP4 |
All of Us Research Program, |
RCV004010989 | SCV004834852 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 825 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSC2-related disorders in the literature. This variant has been identified in 4/282390 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |