ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.389G>A (p.Gly130Asp)

gnomAD frequency: 0.00001  dbSNP: rs72656360
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
Invitae RCV002231244 SCV000627346 pathogenic Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2024-01-01 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 130 of the COL1A2 protein (p.Gly130Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features consistent with autosomal dominant osteogenesis imperfecta (PMID: 17078022, 24342908; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 456836). 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 with a positive predictive value of 95%. 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). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000991603 SCV001143200 pathogenic not provided 2019-08-07 criteria provided, single submitter clinical testing The variant disrupts a glycine residue in the canonical Gly-X-Y repeats of the triple helix domain, which are required for stability and structure of this protein. Therefore it is expected to severely affect the function of the protein. Found in at least one symptomatic patient, and not found in general population data. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid.
GeneDx RCV000991603 SCV001823955 pathogenic not provided 2022-12-19 criteria provided, single submitter clinical testing Identified in patients with osteogenesis imperfecta referred for genetic testing at GeneDx and in published literature (Marini et al., 2007); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain and replaces the glycine in the canonical GlyX-Y repeat; missense substitution of a canonical glycine residue is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (HGMD); This variant is associated with the following publications: (PMID: 25525159, 24342908, 35163361, 17078022)
Revvity Omics, Revvity RCV000991603 SCV002017440 pathogenic not provided 2021-06-03 criteria provided, single submitter clinical testing

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.