Submissions for variant NM_001943.5(DSG2):c.2375_2379dup (p.Asp794fs)

gnomAD frequency: 0.00001  dbSNP: rs773328409

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001864753	SCV002124485	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2021-09-04	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with DSG2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Asp794Profs*16) in the DSG2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 325 amino acid(s) of the DSG2 protein. 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; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002482496	SCV002796577	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB	2021-09-27	criteria provided, single submitter	clinical testing