Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617175 | SCV000736081 | uncertain significance | Cardiovascular phenotype | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.R479C variant (also known as c.1435C>T), located in coding exon 10 of the DSC2 gene, results from a C to T substitution at nucleotide position 1435. The arginine at codon 479 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Color Diagnostics, |
RCV001185003 | SCV001351122 | likely benign | Cardiomyopathy | 2025-03-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001860367 | SCV002312990 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 479 of the DSC2 protein (p.Arg479Cys). This variant is present in population databases (rs138761522, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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 not expected to disrupt DSC2 protein function with a negative 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. |
| All of Us Research Program, |
RCV004002651 | SCV004816158 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2024-02-22 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 479 of the DSC2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/251214 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |