ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.610G>C (p.Glu204Gln)

dbSNP: rs758853661
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000695732 SCV000824247 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 204 of the VHL protein (p.Glu204Gln). This variant is present in population databases (rs758853661, gnomAD 0.004%). 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: 573929). 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 expected to disrupt VHL protein function with a positive predictive value of 80%. 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268256 SCV002552408 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV003303150 SCV003999527 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-22 criteria provided, single submitter clinical testing The p.E204Q variant (also known as c.610G>C), located in coding exon 3 of the VHL gene, results from a G to C substitution at nucleotide position 610. The glutamic acid at codon 204 is replaced by glutamine, 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.
All of Us Research Program, National Institutes of Health RCV003999641 SCV004841672 uncertain significance Von Hippel-Lindau syndrome 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glutamine at codon 204 of the VHL protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/251336 chromosomes 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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