Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000476262 | SCV000551488 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2018-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 398 of the DSC2 protein (p.Gly398Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 410652). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV003380578 | SCV004097118 | uncertain significance | Cardiovascular phenotype | 2023-07-24 | criteria provided, single submitter | clinical testing | The p.G398S variant (also known as c.1192G>A), located in coding exon 9 of the DSC2 gene, results from a G to A substitution at nucleotide position 1192. The glycine at codon 398 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |