Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002231024 | SCV000627356 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2017-02-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 262 of the COL1A2 protein (p.Gly262Arg). 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) and has not been reported in the literature in individuals with a COL1A2-related disease. 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 is expected to be pathogenic. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. 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). |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002244998 | SCV002512474 | likely pathogenic | Osteogenesis imperfecta with normal sclerae, dominant form | 2021-06-08 | criteria provided, single submitter | clinical testing |