Submissions for variant NM_004415.4(DSP):c.3221C>T (p.Ala1074Val)

gnomAD frequency: 0.00001  dbSNP: rs745849763

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001323488	SCV001514407	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2022-09-01	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004005119	SCV004819694	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2023-08-08	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 1074 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 32041989). This variant has been identified in 2/282448 chromosomes 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.