Submissions for variant NM_001943.5(DSG2):c.2761_2764dup (p.Thr922fs)

dbSNP: rs1567934720

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000687935	SCV000815528	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2023-01-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr922Serfs*6) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 197 amino acid(s) of the DSG2 protein. This variant is not present in population databases (gnomAD no frequency). 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: 567765). This variant has not been reported in the literature in individuals affected with DSG2-related conditions.
CeGaT Center for Human Genetics Tuebingen	RCV003326488	SCV004033610	likely pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	DSG2: PVS1:Strong, PM2, PS4:Supporting