Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000821960 | SCV000962736 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-08-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 663976). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 442 of the DSC2 protein (p.Pro442Ser). This variant is present in population databases (rs201480399, 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSC2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003169028 | SCV003853617 | uncertain significance | Cardiovascular phenotype | 2023-01-01 | criteria provided, single submitter | clinical testing | The p.P442S variant (also known as c.1324C>T), located in coding exon 10 of the DSC2 gene, results from a C to T substitution at nucleotide position 1324. The proline at codon 442 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330965 | SCV004038566 | uncertain significance | not specified | 2023-08-19 | criteria provided, single submitter | clinical testing |