Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025058 | SCV001187180 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.Q209R variant (also known as c.626A>G), located in coding exon 3 of the VHL gene, results from an A to G substitution at nucleotide position 626. The glutamine at codon 209 is replaced by arginine, an amino acid with highly similar properties. This alteration (designated as Gln209Arg) was previously reported in an individual with a clinical diagnosis of VHL and a personal history of CNS hemangioblastoma and pancreatic cyst; however, a deletion involving the entire VHL gene was also detected in this individual (Huang JS et al. Eur. J. Clin. Invest., 2007 Jun;37:492-500). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002550907 | SCV003494127 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-06-04 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on VHL protein function. ClinVar contains an entry for this variant (Variation ID: 826280). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 209 of the VHL protein (p.Gln209Arg). |