Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002527011 | SCV003440072 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-08-20 | criteria provided, single submitter | clinical testing | 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). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 265 of the COL1A2 protein (p.Gly265Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 26177859). ClinVar contains an entry for this variant (Variation ID: 425660). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). For these reasons, this variant has been classified as Pathogenic. |
| Department of Medical Sciences, |
RCV000490663 | SCV000574664 | pathogenic | Osteogenesis imperfecta type I | no assertion criteria provided | clinical testing |