Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002240331 | SCV001216943 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with COL1A2-related conditions. This sequence change replaces glycine with arginine at codon 181 of the COL1A2 protein (p.Gly181Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |