Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039407 | SCV000063091 | uncertain significance | not specified | 2012-05-10 | criteria provided, single submitter | clinical testing | The Gly50Asp variant in DSC2 has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is need ed to fully assess the clinical significance of this variant. |
| Invitae | RCV000800605 | SCV000940331 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 50 of the DSC2 protein (p.Gly50Asp). This variant is present in population databases (rs397517391, gnomAD 0.008%). 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: 46166). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DSC2 protein function with a positive predictive value of 80%. 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. |
| Color Diagnostics, |
RCV001177611 | SCV001341850 | uncertain significance | Cardiomyopathy | 2023-03-09 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 50 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 9/282702 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. |
| Ambry Genetics | RCV002390167 | SCV002701434 | likely benign | Cardiovascular phenotype | 2022-07-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001177611 | SCV004240487 | uncertain significance | Cardiomyopathy | 2023-03-13 | criteria provided, single submitter | clinical testing |