Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003771867 | SCV004569649 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with clinical features of von Hippel-Lindau syndrome (PMID: 28781534; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 82 of the VHL protein (p.Arg82Gly). ClinVar contains an entry for this variant (Variation ID: 1297059). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg82 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2362675, 10823831, 11739384, 12603429, 20447124, 23327821, 26973240). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Clinical Genomics Labs, |
RCV001724795 | SCV001950151 | uncertain significance | Von Hippel-Lindau syndrome | 2017-06-21 | no assertion criteria provided | clinical testing |