ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.65A>G (p.Glu22Gly)

dbSNP: rs2125124570
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001898786 SCV002169864 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 22 of the VHL protein (p.Glu22Gly). 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: 1403440). 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 glycine 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.
Ambry Genetics RCV002361206 SCV002662701 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-20 criteria provided, single submitter clinical testing The p.E22G variant (also known as c.65A>G), located in coding exon 1 of the VHL gene, results from an A to G substitution at nucleotide position 65. The glutamic acid at codon 22 is replaced by glycine, 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.
All of Us Research Program, National Institutes of Health RCV004010826 SCV004831112 uncertain significance Von Hippel-Lindau syndrome 2023-09-17 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 22 of the VHL protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with VHL-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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