Submissions for variant NM_004415.4(DSP):c.479G>A (p.Arg160Gln)

gnomAD frequency: 0.00001  dbSNP: rs752941845

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414584	SCV000492358	uncertain significance	not specified	2016-12-08	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the DSP gene. The R160Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R160Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis suggests that this variant is probably damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473264	SCV000543220	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2025-01-23	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852567	SCV000995268	uncertain significance	Ventricular tachycardia	2018-04-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001191134	SCV001358837	uncertain significance	Cardiomyopathy	2024-03-06	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 160 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/282594 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.
All of Us Research Program, National Institutes of Health	RCV003995925	SCV004827227	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2023-10-23	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 160 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/282594 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.
Ambry Genetics	RCV004992196	SCV005575908	likely benign	Cardiovascular phenotype	2024-09-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.