ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6497G>A (p.Arg2166Gln) (rs771692503)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479255 SCV000574395 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing The R2166Q variant has not been published as pathogenic or been reported as benign to our knowledge. The R2166Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R2166Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Though this substitution occurs at a position that is conserved in most mammals, Q2166 is wild-type for at least one mammalian and one non-mammalian species. Furthermore, the majority of in silico analyses predict this variant likely does not alter the protein structure/function.
Invitae RCV000796935 SCV000936470 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-07-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2166 of the DSP protein (p.Arg2166Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs771692503, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 424574). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.