ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8276G>A (p.Arg2759His)

dbSNP: rs936541705
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001037615 SCV001201039 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-11-03 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 836478). 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. This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2759 of the DSP protein (p.Arg2759His).
Color Diagnostics, LLC DBA Color Health RCV001805981 SCV002052255 uncertain significance Cardiomyopathy 2023-03-09 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 2759 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 1/251304 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.
Ambry Genetics RCV002427486 SCV002680158 uncertain significance Cardiovascular phenotype 2022-05-18 criteria provided, single submitter clinical testing The p.R2759H variant (also known as c.8276G>A), located in coding exon 24 of the DSP gene, results from a G to A substitution at nucleotide position 8276. The arginine at codon 2759 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003329369 SCV004036811 uncertain significance not provided 2023-09-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32155531)
All of Us Research Program, National Institutes of Health RCV004004710 SCV004816636 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 2759 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 1/251304 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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