Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002241594 | SCV001403589 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2019-09-11 | criteria provided, single submitter | clinical testing | 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). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly982 amino acid residue in COL1A2. Other variant(s) that disrupt this residue have been observed in individuals with COL1A2-related conditions (PMID: 17078022, 16786509), which suggests that this may be a clinically significant amino acid residue. This variant has been observed in an individual affected with osteogenesis imperfecta (PMID: 27509835). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 982 of the COL1A2 protein (p.Gly982Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |