Submissions for variant NM_004415.4(DSP):c.3443G>A (p.Cys1148Tyr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004806575	SCV005428898	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2024-05-30	criteria provided, single submitter	clinical testing	This missense variant replaces cysteine with tyrosine at codon 1148 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 DSP-related 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.
Ambry Genetics	RCV004994481	SCV005570912	uncertain significance	Cardiovascular phenotype	2024-11-23	criteria provided, single submitter	clinical testing	The p.C1148Y variant (also known as c.3443G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 3443. The cysteine at codon 1148 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.