Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799472 | SCV000939136 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-08-10 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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: 645405). 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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 102 of the VHL protein (p.Pro102Leu). |
| Gene |
RCV003322824 | SCV004028278 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Verma2016[article]) |
| All of Us Research Program, |
RCV004001627 | SCV004822000 | uncertain significance | Von Hippel-Lindau syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004678831 | SCV005179647 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-16 | criteria provided, single submitter | clinical testing | The p.P102L variant (also known as c.305C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 305. The proline at codon 102 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |