Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001938449 | SCV002197044 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-08-10 | criteria provided, single submitter | clinical testing | 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. 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 COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1417546). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 27748872). This variant is present in population databases (rs200663095, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1258 of the COL1A2 protein (p.Arg1258His). |
Gene |
RCV002291786 | SCV002584345 | uncertain significance | not provided | 2022-10-06 | criteria provided, single submitter | clinical testing | Reported in a patient with familial osteogenesis imperfecta (Zhang et al., 2016) and a patient with pulmonary arterial hypertension and ventricular septal defect (Zhu et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD); This variant is associated with the following publications: (PMID: 27748872, 30029678) |