Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000247972 | SCV000320573 | uncertain significance | Cardiovascular phenotype | 2015-11-25 | criteria provided, single submitter | clinical testing | The p.K901R variant (also known as c.2702A>G), located in coding exon 15 of the DSG2 gene, results from an A to G substitution at nucleotide position 2702. The lysine at codon 901 is replaced by arginine, 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), and 1000 Genomes Project. In the ESP, this variant was not observed in 5998 samples (11996 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 is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV001056576 | SCV001221026 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-05-15 | 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 DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 264559). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 901 of the DSG2 protein (p.Lys901Arg). |
| Fulgent Genetics, |
RCV002487164 | SCV002778443 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-08-30 | criteria provided, single submitter | clinical testing |