ClinVar

Description

The c.2955delT variant, located in coding exon 15 of the DSG2 gene, results from a deletion of one nucleotide at nucleotide position 2955, causing a translational frameshift with a predicted alternate stop codon (p.V986Wfs*6). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of DSG2, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 133 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time; however, downstream truncations have been reported in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Christensen AH et al. J. Med. Genet., 2010 Nov;47:736-44; Lahtinen AM et al. Heart Rhythm, 2011 Aug;8:1214-21; Rasmussen TB et al. Hum. Mutat., 2013 May;34:697-705; Baskin B et al. Hum. Genet., 2013 Nov;132:1245-52). This variant was seen in an exome cohort, but cardiovascular history was not provided (Thompson ML et al. Genet. Med., 2018 Apr;[Epub ahead of print]). Based on the majority of available evidence to date, this variant is likely to be pathogenic.