Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059157 | SCV001223769 | pathogenic | Osteogenesis imperfecta type I | 2019-01-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with osteogenesis imperfecta type 3 or 4 (PMID: 27509835). This variant is also known as Gly973Ser in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 1151 of the COL1A1 protein (p.Gly1151Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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 COL1A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). |