ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6137T>G (p.Val2046Gly)

gnomAD frequency: 0.00001  dbSNP: rs746016404
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001071567 SCV001236876 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 2046 of the DSP protein (p.Val2046Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs746016404, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Color Diagnostics, LLC DBA Color Health RCV001177105 SCV001341239 uncertain significance Cardiomyopathy 2023-09-05 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 2046 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 been reported in an individual affected with dilated cardiomyopathy (PMID: 32880476). This variant has been identified in 1/250926 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 RCV004000202 SCV004814257 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 2046 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 been reported in an individual affected with dilated cardiomyopathy (PMID: 32880476). This variant has been identified in 1/250926 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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