Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003805187 | SCV004606878 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 1076 of the COL1A2 protein (p.Pro1076His). This variant is present in population databases (rs12666875, gnomAD 0.03%). This missense change has been observed in individual(s) with autosomal dominant osteogenesis imperfecta and/or clinical features of COL1A2-related conditions (PMID: 30715774, 33942288). 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 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |