Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002434966 | SCV002745111 | uncertain significance | Cardiovascular phenotype | 2022-09-06 | criteria provided, single submitter | clinical testing | The p.E852* variant (also known as c.2554G>T), located in coding exon 15 of the DSG2 gene, results from a G to T substitution at nucleotide position 2554. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of theDSG2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 23% of the protein. The exact functional effect of this alteration is unknown, and loss of function alterations in this region of the DSG2 gene are more common in population databases than expected for likely pathogenic/disease-causing variants (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003101965 | SCV003500720 | pathogenic | Arrhythmogenic right ventricular dysplasia 10 | 2022-09-27 | 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. This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu852*) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 267 amino acid(s) of the DSG2 protein. |