Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002241124 | SCV001388019 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-11-30 | 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 948 of the COL1A2 protein (p.Arg948Cys). This variant is present in population databases (rs779303344, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 945567). 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 95%. 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. |
| Fulgent Genetics, |
RCV002480710 | SCV002799580 | uncertain significance | Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, cardiac valvular type; Osteoporosis; Ehlers-danlos syndrome, arthrochalasia type, 2; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 | 2022-02-14 | criteria provided, single submitter | clinical testing |