ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.7331G>C (p.Arg2444Pro) (rs895701604)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559787 SCV000657397 uncertain significance Bethlem myopathy 1 2018-08-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 2444 of the COL6A3 protein (p.Arg2444Pro). The arginine residue is highly 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 COL6A3-related disease. This variant occurs with a pathogenic variant (p.Gln26*) in COL6A3 in an individual affected with muscular dystrophy (Invitae database). Family studies indicate that these two variants are on opposite chromosomes (in trans), which suggests the c.7331G>C substitution may contribute to disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. 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.