ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.2819G>T (p.Gly940Val)

dbSNP: rs1792257312
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269734 SCV001449951 pathogenic not provided 2019-04-02 criteria provided, single submitter clinical testing
Invitae RCV002542860 SCV003440611 pathogenic Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2022-06-14 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 940 of the COL1A2 protein (p.Gly940Val). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 988398). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 27509835).

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