Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520319 | SCV000621764 | uncertain significance | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSG2 gene. The A748S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed at a significant frequency in large population cohorts (Lek et al., 2016). The A748S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and serine (S) is the wild-type residue at this position in at least two species. Additionally, in silico analysis predicts this variant likely does not alter the protein structure/function. |
| Labcorp Genetics |
RCV001222634 | SCV001394743 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-03-16 | criteria provided, single submitter | clinical testing | 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 DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 452916). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 748 of the DSG2 protein (p.Ala748Ser). |
| Ambry Genetics | RCV003159693 | SCV003856002 | uncertain significance | Cardiovascular phenotype | 2023-01-21 | criteria provided, single submitter | clinical testing | The p.A748S variant (also known as c.2242G>T), located in coding exon 14 of the DSG2 gene, results from a G to T substitution at nucleotide position 2242. The alanine at codon 748 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. |