ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.3223C>T (p.Arg1075Trp) (rs201962257)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726400 SCV000344396 uncertain significance not provided 2016-08-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765645 SCV000896974 uncertain significance Bethlem myopathy 1; Ullrich congenital muscular dystrophy 1; Dystonia 27 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000726400 SCV000617175 uncertain significance not provided 2017-09-12 criteria provided, single submitter clinical testing The R1075W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1075W variant is observed in 37/25,768 (0.14%) alleles from individuals of Finnish background in large population cohorts, and in 1 unaffected homozygous individual undergoing testing at GeneDx (Lek et al., 2016). 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 that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with COL6A3-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000653597 SCV000775480 uncertain significance Bethlem myopathy 1 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1075 of the COL6A3 protein (p.Arg1075Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs201962257, ExAC 0.2%). This variant has been observed in an individual unaffected by COL6A3 related conditions (PMID: 26004199). ClinVar contains an entry for this variant (Variation ID: 289937). 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, 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.