Submissions for variant NM_004415.4(DSP):c.925C>T (p.Gln309Ter)

dbSNP: rs1581799453

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853384	SCV000996260	pathogenic	Arrhythmogenic right ventricular dysplasia 8	2019-03-01	criteria provided, single submitter	clinical testing	This nonsense variant found in exon 7 of 24 is predicted to result in loss of normal protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Based on the available evidence, the c.925C>T (p.Gln309Ter) variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003768632	SCV004590076	pathogenic	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln309*) in the DSP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). 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: 692081). For these reasons, this variant has been classified as Pathogenic.