Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494189 | SCV000581846 | uncertain significance | not provided | 2019-01-31 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001856958 | SCV002309334 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2023-05-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1158 of the COL1A2 protein (p.Asn1158Thr). This missense change has been observed in individual(s) with clinical features of osteogenesis imperfecta (Invitae). ClinVar contains an entry for this variant (Variation ID: 429311). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |