Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000811185 | SCV000951439 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2021-07-01 | 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. 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 expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 655083). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 146 of the VHL protein (p.Pro146Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |