Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051992 | SCV001216177 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 569 of the DSG2 protein (p.Gln569His). This variant is present in population databases (rs370097438, gnomAD 0.007%). 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: 848271). 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. |
Color Diagnostics, |
RCV001182990 | SCV001348634 | likely benign | Cardiomyopathy | 2018-12-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002400298 | SCV002712897 | uncertain significance | Cardiovascular phenotype | 2022-04-09 | criteria provided, single submitter | clinical testing | The p.Q569H variant (also known as c.1707G>C), located in coding exon 12 of the DSG2 gene, results from a G to C substitution at nucleotide position 1707. The glutamine at codon 569 is replaced by histidine, an amino acid with highly 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. |