Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003090281 | SCV003479329 | uncertain significance | Osteogenesis imperfecta type I | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1252 of the COL1A1 protein (p.Arg1252Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2166021). 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 not expected to disrupt COL1A1 protein function with a negative 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. |