Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003805279 | SCV004592975 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 107 of the VHL protein (p.Arg107Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of von Hippel-Lindau (VHL) syndrome (PMID: 26230854; Invitae). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg107 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12202531, 19336503). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |