Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001361052 | SCV001557013 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2020-02-26 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with VHL-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 209 of the VHL protein (p.Gln209His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. |
| Ambry Genetics | RCV002357223 | SCV002655899 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-03 | criteria provided, single submitter | clinical testing | The p.Q209H variant (also known as c.627A>T), located in coding exon 3 of the VHL gene, results from an A to T substitution at nucleotide position 627. The glutamine at codon 209 is replaced by histidine, 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. |