Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001248663 | SCV001422168 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 835 of the DSG2 protein (p.Thr835Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 972598). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002451618 | SCV002738816 | uncertain significance | Cardiovascular phenotype | 2022-02-17 | criteria provided, single submitter | clinical testing | The c.2504_2505delCAinsTG variant (also known as p.T835M), located in coding exon 15 of the DSG2 gene, results from an in-frame deletion of CA and insertion of TG at nucleotide positions 2504 to 2505. This results in the substitution of the threonine residue for a methionine residue at codon 835, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |