Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240166 | SCV001208432 | likely pathogenic | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2019-02-10 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel single amino acid in-frame deletion affecting a domain that is critical for normal protein structure, stability and function. This type of in-frame deletion is also highly enriched in affected individuals and expected to be pathogenic. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available for this specific variant. However, 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 and in-frame deletions disrupting these regular Gly-Xaa-Yaa repeats are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). This variant has not been reported in the literature in individuals with COL1A2-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.1394_1396del, results in the deletion of 1 amino acid of the COL1A2 protein (p.Glu465del), but otherwise preserves the integrity of the reading frame. |