Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240338 | SCV001220372 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2020-03-05 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with histidine at codon 1523 of the COL5A1 protein (p.Pro1523His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant has not been reported in the literature in individuals with COL5A1-related conditions. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). |
| Gene |
RCV001759803 | SCV002004964 | uncertain significance | not provided | 2019-07-10 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed 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 X 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 X position is not a common mechanism of disease (Symoens et al., 2012; Stenson et al., 2014) |
| Ai |
RCV001759803 | SCV002502327 | uncertain significance | not provided | 2021-09-09 | criteria provided, single submitter | clinical testing |