ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5942A>G (p.Tyr1981Cys)

dbSNP: rs1085307622
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489261 SCV000576881 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing The Y1981C variant in the DSP gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y1981C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y1981C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y1981C as a variant of uncertain significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769234 SCV000900610 uncertain significance Cardiomyopathy 2017-04-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769234 SCV001340589 uncertain significance Cardiomyopathy 2023-11-01 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 1981 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 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.
Invitae RCV003766745 SCV004570001 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1981 of the DSP protein (p.Tyr1981Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of arrhythmogenic right ventricular cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 30731207). ClinVar contains an entry for this variant (Variation ID: 426436). 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.

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