ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.4325G>A (p.Arg1442Gln) (rs761126767)

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 RCV000198879 SCV000249992 uncertain significance not provided 2018-08-29 criteria provided, single submitter clinical testing The R1442Q variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1442Q variant is observed in 9/276522 (0.003%) alleles in large population cohorts (Lek et al., 2016). The R1442Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret R1442Q as a variant of uncertain significance.
Invitae RCV000794781 SCV000934211 uncertain significance Ehlers-Danlos syndrome, classic type 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1442 of the COL5A2 protein (p.Arg1442Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs761126767, ExAC 0.02%). This variant has not been reported in the literature in individuals with COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213129). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.