Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000631261 | SCV000752289 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-07-06 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 526668). 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 glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 57 of the VHL protein (p.Gly57Ala). |
| Ambry Genetics | RCV004025398 | SCV005036778 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | The p.G57A variant (also known as c.170G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 170. The glycine at codon 57 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |