Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799447 | SCV000939110 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-04-23 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 645385). 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 arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 176 of the VHL protein (p.Arg176Gly). |
| Ambry Genetics | RCV002345780 | SCV002646491 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-14 | criteria provided, single submitter | clinical testing | The p.R176G variant (also known as c.526A>G), located in coding exon 3 of the VHL gene, results from an A to G substitution at nucleotide position 526. The arginine at codon 176 is replaced by glycine, an amino acid with dissimilar 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. |