Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000776434 | SCV000911917 | uncertain significance | Cardiomyopathy | 2023-01-23 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 798 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 7/251166 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. |
| Labcorp Genetics |
RCV001294496 | SCV001483376 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-07-07 | 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: 630584). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs201548399, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 798 of the DSC2 protein (p.Arg798Trp). |
| Ambry Genetics | RCV002424773 | SCV002731963 | uncertain significance | Cardiovascular phenotype | 2021-06-22 | criteria provided, single submitter | clinical testing | The p.R798W variant (also known as c.2392C>T), located in coding exon 15 of the DSC2 gene, results from a C to T substitution at nucleotide position 2392. The arginine at codon 798 is replaced by tryptophan, an amino acid with dissimilar 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. |
| Fulgent Genetics, |
RCV001294496 | SCV002786199 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-10-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004001471 | SCV004816054 | uncertain significance | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-12-01 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 798 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 7/251166 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. |