Submissions for variant NM_004415.4(DSP):c.5384C>A (p.Ser1795Tyr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003794000	SCV004582121	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1795 of the DSP protein (p.Ser1795Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DSP-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV004006035	SCV004816600	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2023-04-03	criteria provided, single submitter	clinical testing	This missense variant replaces serine with tyrosine at codon 1795 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	RCV004366601	SCV004859856	uncertain significance	Cardiovascular phenotype	2023-12-14	criteria provided, single submitter	clinical testing	The c.5384C>A (p.S1795Y) alteration is located in exon 24 (coding exon 24) of the DSP gene. This alteration results from a C to A substitution at nucleotide position 5384, causing the serine (S) at amino acid position 1795 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.