Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002241314 | SCV001396652 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2019-08-01 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL1A2-related conditions. This variant is present in population databases (rs772238510, ExAC 0.02%). This sequence change replaces proline with leucine at codon 444 of the COL1A2 protein (p.Pro444Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
| Gene |
RCV001544615 | SCV001763783 | uncertain significance | not provided | 2020-05-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (Stenson et al., 2014); Has not been previously published as pathogenic or benign to our knowledge |