ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.794G>A (p.Arg265Lys) (rs1064796438)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484781 SCV000573160 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing The R265K variant has not been published as pathogenic or been reported as benign to our knowledge. The R265K variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. The majority of in silico analyses (2 out of 3) predict this variant is probably damaging to the protein structure/function. Nonetheless, the R265K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Invitae RCV000543557 SCV000641349 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-04-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 265 of the DSP protein (p.Arg265Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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