Submissions for variant NM_004415.4(DSP):c.7918_7919dup (p.Ile2641fs)

dbSNP: rs1759606062

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001183151	SCV001348808	uncertain significance	Cardiomyopathy	2019-09-10	criteria provided, single submitter	clinical testing	This variant inserts 2 nucleotides in exon 24 of the DSP gene, creating a frameshift and premature translation stop signal in the last coding exon. To our knowledge, functional studies have not been performed for this variant. 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 disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003770017	SCV004580796	pathogenic	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-05-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile2641Alafs*40) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 231 amino acid(s) of the DSP protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 922850). This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (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.