Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV002247357 | SCV002518737 | pathogenic | Infantile cortical hyperostosis | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000018826 | SCV003442450 | pathogenic | Osteogenesis imperfecta type I | 2022-04-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 272 of the COL1A1 protein (p.Gly272Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 2794057, 30715774). This variant is also known as Gly94Cys. ClinVar contains an entry for this variant (Variation ID: 17285). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL1A1 protein function. This variant disrupts the triple helix domain of COL1A1. 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, 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. |
| OMIM | RCV000018826 | SCV000039109 | pathogenic | Osteogenesis imperfecta type I | 1989-10-01 | no assertion criteria provided | literature only |