Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001888635 | SCV002142686 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2021-09-24 | 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 COL5A2 protein function. This variant has not been reported in the literature in individuals affected with COL5A2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with histidine at codon 1169 of the COL5A2 protein (p.Pro1169His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. |
| Gene |
RCV003235609 | SCV003933464 | uncertain significance | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |