Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063276 | SCV001228114 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-03-16 | 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. This variant disrupts the p.Ile151 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10567493, 11309459, 17024664, 17661816, 28469506). 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: 857570). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 151 of the VHL protein (p.Ile151Val). |
| MGZ Medical Genetics Center | RCV002290579 | SCV002581365 | likely pathogenic | Von Hippel-Lindau syndrome | 2022-02-25 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003160518 | SCV003860987 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-16 | criteria provided, single submitter | clinical testing | The p.I151V variant (also known as c.451A>G), located in coding exon 2 of the VHL gene, results from an A to G substitution at nucleotide position 451. The isoleucine at codon 151 is replaced by valine, 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. |