ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3407G>C (p.Gly1136Ala) (rs1555572013)

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 RCV000559468 SCV000627236 likely pathogenic Osteogenesis imperfecta type I 2017-05-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 1136 of the COL1A1 protein (p.Gly1136Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL1A1-related disease. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL1A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). In summary, this variant is a novel missense change affecting a residue crucial for protein structure and stability. Although additional genetic data will be necessary to further confirm pathogenicity for this variant, glycine substitutions located in COL1A1 triple helix domains are likely deleterious. For these reasons, this variant has been classified as Likely Pathogenic.

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.