Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002460033 | SCV002736738 | uncertain significance | Cardiovascular phenotype | 2022-08-24 | criteria provided, single submitter | clinical testing | The p.T814S variant (also known as c.2440A>T), located in coding exon 15 of the DSC2 gene, results from an A to T substitution at nucleotide position 2440. The threonine at codon 814 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. |
| Invitae | RCV003631268 | SCV004378349 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 814 of the DSC2 protein (p.Thr814Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 1791325). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. |