Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003785065 | SCV004578071 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 926 of the COL1A2 protein (p.Arg926Cys). This variant is present in population databases (rs745363291, gnomAD 0.01%). This missense change has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 35723357). 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. 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. |