Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001756962 | SCV001995223 | uncertain significance | not provided | 2020-05-14 | 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 that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Occurs at a non-Glycine residue within the collagen triple-helical region containing Gly-X-Y repeats, however, substitutions of Glycine residues in these Gly-X-Y motifs within the triple helical regions of the protein represent the vast majority of pathogenic missense variants (Stenson et al., 2014) |
Invitae | RCV001868459 | SCV002109489 | uncertain significance | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2021-11-27 | 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: 1309894). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 944 of the COL1A2 protein (p.His944Tyr). |