Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000618341 | SCV000736230 | uncertain significance | Cardiovascular phenotype | 2016-03-30 | criteria provided, single submitter | clinical testing | The p.D326V variant (also known as c.977A>T), located in coding exon 8 of the DSG2 gene, results from an A to T substitution at nucleotide position 977. The aspartic acid at codon 326 is replaced by valine, an amino acid with highly dissimilar properties. This variant was detected in a patient reported to have arrhythmogenic right ventricular dysplasia/cardiomyopathy, who also had a nonsense alteration in the PKP2 gene (Fressart V et al. Europace. 2010;12(6):861-8). Based on data from ExAC, the T allele was reported in 2 of 120684 (0.001%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed March 21, 2016]). 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 5971 samples (11942 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Invitae | RCV001067163 | SCV001232206 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-08-31 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 518781). This missense change has been observed in individual(s) with clinical features of DSG2-related conditions (PMID: 20400443). This variant is present in population databases (rs769699241, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 326 of the DSG2 protein (p.Asp326Val). |
Fulgent Genetics, |
RCV002506496 | SCV002814539 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-08-17 | criteria provided, single submitter | clinical testing |