ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.2288G>A (p.Gly763Asp)

dbSNP: rs72658179
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001941895 SCV002231928 pathogenic Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2021-03-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL1A2. 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 COL1A2, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL1A2 protein function. This variant has been observed in individual(s) with osteogenesis imperfecta type III (PMID: 26627451, 21488294). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 763 of the COL1A2 protein (p.Gly763Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243493 SCV002512441 likely pathogenic Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III 2021-05-13 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 supporting, PM1 supporting, PM2 moderate, PM6 supporting, PP3 supporting, PP4 supporting

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.