ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3763A>G (p.Arg1255Gly)

dbSNP: rs1477870659
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521754 SCV000620846 uncertain significance not provided 2020-06-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Color Diagnostics, LLC DBA Color Health RCV001524975 SCV001734961 uncertain significance Cardiomyopathy 2020-05-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 1255 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 cardiovascular disorders in the literature. This variant has been identified in 1/250726 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 RCV001858019 SCV002318221 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-07-03 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 452071). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1255 of the DSP protein (p.Arg1255Gly).
All of Us Research Program, National Institutes of Health RCV004806391 SCV005428908 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-08-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV004992306 SCV005575918 uncertain significance Cardiovascular phenotype 2024-09-30 criteria provided, single submitter clinical testing The p.R1255G variant (also known as c.3763A>G), located in coding exon 23 of the DSP gene, results from an A to G substitution at nucleotide position 3763. The arginine at codon 1255 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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