Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003119286 | SCV003790251 | pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2022-07-31 | criteria provided, single submitter | clinical testing | This variant results in the deletion of exon 15 and part of exons 14 and 16 (c.690_788del) of the COL1A2 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. 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). For these reasons, this variant has been classified as Pathogenic. |