Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001240444 | SCV001413387 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-03-03 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 965895). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is present in population databases (rs121913347, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 208 of the VHL protein (p.His208Tyr). |
| Ambry Genetics | RCV002366062 | SCV002658494 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-15 | criteria provided, single submitter | clinical testing | The p.H208Y variant (also known as c.622C>T), located in coding exon 3 of the VHL gene, results from a C to T substitution at nucleotide position 622. The histidine at codon 208 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is poorly 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. |