ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7186T>A (p.Tyr2396Asn)

dbSNP: rs863225268
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV000201903 SCV000256649 uncertain significance Paroxysmal familial ventricular fibrillation 2015-08-12 criteria provided, single submitter research The DSP Tyr2396Asn is a novel variant. It is absent from both the 1000 genomes project (http://www.1000genomes.org/), and the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We identified this variant in a clinically unaffected female, whose brother has idiopathic VF. Both patients also have a second variant (LMNA Thr27Ser) which is classified as a variant of "uncertain significance". Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect. Based on its absence in the general population and our limited familial data, we classify DSP Tyr2396Asn as variant of "uncertain significance".
Labcorp Genetics (formerly Invitae), Labcorp RCV002515479 SCV003352257 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-04-20 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2396 of the DSP protein (p.Tyr2396Asn). This variant has not been reported in the literature in individuals affected with DSP-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 217831).
All of Us Research Program, National Institutes of Health RCV003997039 SCV004831011 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with asparagine at codon 2396 of the DSP protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 been identified in 1/251450 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.

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