Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001380806 | SCV001578986 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2022-11-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DSG2 protein in which other variant(s) (p.Glu1020Alafs*18) have been determined to be pathogenic (PMID: 20864495, 21397041, 23381804). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1069061). 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 0.006%). This sequence change creates a premature translational stop signal (p.Glu1018Glyfs*20) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 101 amino acid(s) of the DSG2 protein. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282534 | SCV002572293 | likely pathogenic | Cardiomyopathy | 2022-08-24 | criteria provided, single submitter | clinical testing | Variant summary: DSG2 c.3052dupG (p.Glu1018GlyfsX20), located in the last exon (stop codon spans c.3355 to c.3357 at position 1119), results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 249390 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3052dupG in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV001380806 | SCV003835832 | likely pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2022-10-20 | criteria provided, single submitter | clinical testing |