Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000710787 | SCV000841091 | pathogenic | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001861953 | SCV002268204 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 130 of the COL1A2 protein (p.Gly130Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant COL1A2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 585504). 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 COL1A2 protein function with a positive predictive value of 95%. This variant disrupts the triple helix domain of COL1A2. 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). This variant disrupts the p.Gly130 amino acid residue in COL1A2. Other variant(s) that disrupt this residue have been observed in individuals with COL1A2-related conditions (PMID: 17078022, 24342908; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV005034334 | SCV005669774 | likely pathogenic | Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, cardiac valvular type; Osteoporosis; Ehlers-danlos syndrome, arthrochalasia type, 2; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 | 2023-12-27 | criteria provided, single submitter | clinical testing |