ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6325G>A (p.Glu2109Lys)

gnomAD frequency: 0.00001  dbSNP: rs397516951
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038073 SCV000061739 uncertain significance not specified 2012-05-03 criteria provided, single submitter clinical testing The Glu2109Lys variant in DSP has not been reported in the literature and has no t been detected in a large and broad population screened by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS). This variant has been identi fied in 1 individual with DCM tested by our laboratory. Computational analyses ( biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. The low population frequency of this variant supports a pathogenic role but is insuffici ent to establish this with certainty. Additional information is needed to fully assess the clinical significance of the Glu2109Lys variant.
Color Diagnostics, LLC DBA Color Health RCV001178854 SCV001343407 uncertain significance Cardiomyopathy 2023-07-21 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 2109 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 been identified in 2/251414 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003764678 SCV004574904 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-08-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2109 of the DSP protein (p.Glu2109Lys). This variant is present in population databases (rs397516951, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 44937). 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 RCV003996352 SCV004825851 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 2109 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 been identified in 2/251414 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.
Mayo Clinic Laboratories, Mayo Clinic RCV004791244 SCV005412003 uncertain significance not provided 2024-07-16 criteria provided, single submitter clinical testing

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