Submissions for variant NM_001943.5(DSG2):c.2857del (p.Leu953fs)

dbSNP: rs2073308127

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001183356	SCV001349072	uncertain significance	Cardiomyopathy	2022-09-12	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in the last exon (exon 15) of the DSG2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in autosomal dominant cardiomyopathy conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001537874	SCV001754776	likely pathogenic	Arrhythmogenic right ventricular dysplasia 10	2019-09-26	criteria provided, single submitter	clinical testing	The c.2857delC (p.Leu953TrpfsTer11) variant in the DSG2 gene is predicted to introduce a premature translation termination codon. It is predicted to cause loss of normal protein function either through abnormal, prematurely truncated protein, or by absence of protein product due to nonsense-mediated mRNA decay. This variant was not observed in the gnomAD database. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 23381804, 21397041). For these reasons, this variant has been classified as Likely Pathogenic.