Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001861725 | SCV002245368 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 548666). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 16705691, 26177859, 26788535, 30715774, 31429852). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 676 of the COL1A2 protein (p.Gly676Asp). |
| Yale Center for Mendelian Genomics, |
RCV000662309 | SCV000784640 | likely pathogenic | Dentinogenesis imperfecta | 2016-01-08 | no assertion criteria provided | literature only |