ClinVar

Description

This variant changes 1 nucleotide in exon 23 of the DSP gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. A study with skin biopsies from carrier individuals has shown that this variant causes an absent expression of the major DSP transcript (NM_004415) in the heart (PMID: 16467215). This variant has been reported in homozygous state in an individual affected with arrhythmogenic cardiomyopathy with epidermolytic palmoplantar keratoderma and wooly hair (PMID: 16467215), and in compound heterozygous state with another DSP pathogenic variant in an individual affected with arrhythmogenic-dilated cardiomyopathy with epidermolytic palmoplantar keratoderma and wooly hair (PMID: 30993396). This variant has also been reported in compound heterozygous state with a DSP variant of uncertain significance in two twin brothers affected with early-onset dilated cardiomyopathy (PMID: 30398466), and in heterozygous state in an individual suspected of having hereditary cardiomyopathy (PMID: 35083019) as well as in five asymptomatic individuals (PMID: 16467215, 30398466, 30993396). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of DSP function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.