Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002406262 | SCV002712438 | uncertain significance | Cardiovascular phenotype | 2020-08-19 | criteria provided, single submitter | clinical testing | The p.S566R variant (also known as c.1698T>A), located in coding exon 12 of the DSG2 gene, results from a T to A substitution at nucleotide position 1698. The serine at codon 566 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003408273 | SCV004108174 | uncertain significance | DSG2-related disorder | 2023-06-19 | criteria provided, single submitter | clinical testing | The DSG2 c.1698T>A variant is predicted to result in the amino acid substitution p.Ser566Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Labcorp Genetics |
RCV003631262 | SCV004551402 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 566 of the DSG2 protein (p.Ser566Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1778277). 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 DSG2 protein function with a negative predictive value of 95%. 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. |