Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000248776 | SCV000319938 | uncertain significance | Cardiovascular phenotype | 2015-07-21 | criteria provided, single submitter | clinical testing | The p.I233V variant (also known as c.697A>G), located in coding exon 6 of the DSC2 gene, results from an A to G substitution at nucleotide position 697. The isoleucine at codon 233 is replaced by valine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), the Exome Aggregation Consortium (ExAC) and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. 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 for this variant is limited at this time, its clinical significance is unclear. |
| Invitae | RCV003631099 | SCV004372889 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-05-12 | criteria provided, single submitter | clinical testing | 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: 264192). 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 0.002%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 233 of the DSC2 protein (p.Ile233Val). 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. |