ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2894G>C (p.Arg965Pro) (rs201854898)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000254951 SCV000344670 uncertain significance not provided 2018-04-02 criteria provided, single submitter clinical testing
GeneDx RCV000254951 SCV000322501 likely pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing The R965P variant in the COL6A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R965P variant has been observed with a pathogenic variant on the opposite allele (in trans) in a patient referred for genetic testing at GeneDx with features suggestive of a COL6A2-related disorder. The R965P variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R965P 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R965P as a likely pathogenic variant.
Invitae RCV000560338 SCV000657185 uncertain significance Bethlem myopathy 1 2017-03-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 965 of the COL6A2 protein (p.Arg965Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL6A2-related disease. ClinVar contains an entry for this variant (Variation ID: 265525). 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 rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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.