ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3763A>G (p.Arg1255Gly) (rs1477870659)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521754 SCV000620846 uncertain significance not provided 2017-09-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSP gene. The R1255G variant has not been published as pathogenic or been reported as benign to our knowledge. Although a different missense variant at the same residue (R1255K) has been reported in association with ARVC, the clinical significance of this variant remains unknown (Bauce et al., 2005; Xu et al., 2010; Walsh et al., 2017). The R1255G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where only amino acids with similar properties to arginine are tolerated across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R1255G variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.

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