Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520286 | SCV000621979 | uncertain significance | not provided | 2017-11-01 | criteria provided, single submitter | clinical testing | The P566L variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P566L variant is not observed in large population cohorts (Lek et al., 2016). The P566L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P566L as a variant of uncertain significance. |
Invitae | RCV002231216 | SCV000631569 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 566 of the COL5A2 protein (p.Pro566Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL5A2-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. 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 COL5A2 protein function. ClinVar contains an entry for this variant (Variation ID: 453117). |