Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002232840 | SCV000813677 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2017-12-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with COL1A2-related disease. 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). In summary, this variant is a novel missense change affecting a residue that is known to be critical for normal protein structure, stability and function. This type of missense change is also highly enriched in affected individuals and expected to be pathogenic. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 250 of the COL1A2 protein (p.Gly250Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |