Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001189683 | SCV001357027 | uncertain significance | Cardiomyopathy | 2020-02-10 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 634 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/250242 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. |
| Ambry Genetics | RCV003163470 | SCV003853628 | uncertain significance | Cardiovascular phenotype | 2023-03-08 | criteria provided, single submitter | clinical testing | The p.R634C variant (also known as c.1900C>T), located in coding exon 13 of the DSC2 gene, results from a C to T substitution at nucleotide position 1900. The arginine at codon 634 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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. |