ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.191G>A (p.Arg64His)

dbSNP: rs104893826
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000123103 SCV000166404 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-08-02 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 135952). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 64 of the VHL protein (p.Arg64His).
GeneDx RCV001588972 SCV001816271 uncertain significance not provided 2019-06-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV004567063 SCV005055806 uncertain significance Chuvash polycythemia 2023-12-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV004678616 SCV005179651 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-10 criteria provided, single submitter clinical testing The p.R64H variant (also known as c.191G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 191. The arginine at codon 64 is replaced by histidine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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.