ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.3331G>A (p.Ala1111Thr) (rs151021451)

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 RCV000725760 SCV000339227 uncertain significance not provided 2016-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000725760 SCV000620584 uncertain significance not provided 2017-09-07 criteria provided, single submitter clinical testing The A1111T variant in the COL6A3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1111T variant is observed in 6/10344 (0.06%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). The A1111T 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 where amino acids with similar properties to Alanine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A1111T as a variant of uncertain significance.
Invitae RCV000801843 SCV000941641 uncertain significance Bethlem myopathy 1 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1111 of the COL6A3 protein (p.Ala1111Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs151021451, ExAC 0.06%). This variant has not been reported in the literature in individuals with COL6A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 285984). 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 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.