ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.139G>A (p.Glu47Lys)

gnomAD frequency: 0.00001  dbSNP: rs1457039250
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815458 SCV000955912 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-08-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 47 of the VHL protein (p.Glu47Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 658604). 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.
Ambry Genetics RCV002390655 SCV002697708 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-31 criteria provided, single submitter clinical testing The p.E47K variant (also known as c.139G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 139. The glutamic acid at codon 47 is replaced by lysine, 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.
Baylor Genetics RCV003461232 SCV004206471 uncertain significance Chuvash polycythemia 2023-10-08 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001780 SCV004832661 uncertain significance Von Hippel-Lindau syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 47 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 been identified in 1/175198 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.