Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002239314 | SCV001204525 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2020-02-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). This variant has been observed in individual(s) with osteogenesis imperfecta (PMID: 21520333, 26551090, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 118 of the COL1A2 protein (p.Gly118Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |
| Gene |
RCV001563459 | SCV001786406 | pathogenic | not provided | 2023-05-03 | criteria provided, single submitter | clinical testing | 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); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26551090) |