Submissions for variant NM_001943.5(DSG2):c.1750C>T (p.Gln584Ter)

gnomAD frequency: 0.00001  dbSNP: rs794728086

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227785	SCV000287231	pathogenic	Arrhythmogenic right ventricular dysplasia 10	2023-06-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 199810). 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.Gln584*) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562).
All of Us Research Program, National Institutes of Health	RCV003996618	SCV004841985	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 12 of the DSG2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 31386562). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion for a pathogenic role, clinical significance of loss-of-function DSG2 variants in autosomal dominant arrhythmogenic cardiomyopathy is not yet clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.