Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001187011 | SCV001353667 | uncertain significance | Cardiomyopathy | 2022-11-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with isoleucine at codon 621 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31374 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001859121 | SCV002158505 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-12-23 | 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 DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 925187). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 621 of the DSC2 protein (p.Arg621Ile). |
Ambry Genetics | RCV002411708 | SCV002719895 | uncertain significance | Cardiovascular phenotype | 2021-08-22 | criteria provided, single submitter | clinical testing | The p.R621I variant (also known as c.1862G>T), located in coding exon 12 of the DSC2 gene, results from a G to T substitution at nucleotide position 1862. The arginine at codon 621 is replaced by isoleucine, 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. |