Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001214107 | SCV001385772 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2019-10-17 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the DSG2 gene (p.Tyr799*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 320 amino acids of the DSG2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSG2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the DSG2 protein. Other variant(s) that disrupt this region (p.Glu1020Alafs*18) have been determined to be pathogenic (PMID: 21397041, 20864495, 23381804). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |