ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3094G>A (p.Ala1032Thr) (rs374095521)

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 RCV000497329 SCV000589955 uncertain significance not provided 2017-06-02 criteria provided, single submitter clinical testing The A1032T variant in the COL1A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1032T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1032T 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. However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A1032T as a variant of uncertain significance.
Invitae RCV000631498 SCV000752580 uncertain significance Osteogenesis imperfecta type I 2017-10-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1032 of the COL1A1 protein (p.Ala1032Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs374095521, ExAC 0.02%). This variant has not been reported in the literature in individuals with COL1A1-related disease. ClinVar contains an entry for this variant (Variation ID: 432245). 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 tolerated, 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.