Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002235432 | SCV000963503 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2018-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 700 of the COL1A2 protein (p.Gly700Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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, missense variants at 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. Disruption of this glycine residue has been observed in individuals affected with osteogenesis imperfecta (PMID: 27509835, 17078022, 19594296). This residue is also referred to as p.Gly610 in the literature. This variant is not present in population databases (ExAC no frequency). |