Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000471372 | SCV000553419 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 61 of the VHL protein (p.Pro61Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 411990). 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. 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. |
| Counsyl | RCV000663198 | SCV000786374 | uncertain significance | Von Hippel-Lindau syndrome | 2018-04-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001013302 | SCV001173872 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-03 | criteria provided, single submitter | clinical testing | The p.P61S variant (also known as c.181C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 181. The proline at codon 61 is replaced by serine, an amino acid with similar properties. This amino acid position is well 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. |