Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015609 | SCV001176458 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-22 | criteria provided, single submitter | clinical testing | The p.R82H variant (also known as c.245G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 245. The arginine at codon 82 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001219698 | SCV001391648 | likely pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-02-21 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 12202531, 12603429, 20447124, 23327821, 23626751, 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. ClinVar contains an entry for this variant (Variation ID: 821314). This missense change has been observed in individual(s) with pheochromocytoma (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 82 of the VHL protein (p.Arg82His). |