Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001318363 | SCV001509061 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2018-06-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 49 of the VHL protein (p.Gly49Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with VHL-related disease. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |