ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.116G>A (p.Gly39Asp)

gnomAD frequency: 0.00001  dbSNP: rs368473853
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531510 SCV000626879 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 39 of the VHL protein (p.Gly39Asp). 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: 456570). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VHL 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.
All of Us Research Program, National Institutes of Health RCV004003772 SCV004839598 uncertain significance Von Hippel-Lindau syndrome 2023-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023755 SCV005036776 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing The p.G39D variant (also known as c.116G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 116. The glycine at codon 39 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is not 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.

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