ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.14C>T (p.Ala5Val) (rs755333116)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195431 SCV000254649 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 5 of the VHL protein (p.Ala5Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs755333116, ExAC 0.02%). This variant has not been reported in the literature in individuals with VHL-related disease. ClinVar contains an entry for this variant (Variation ID: 216476). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Counsyl RCV000409910 SCV000489266 uncertain significance Von Hippel-Lindau syndrome 2016-09-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000492641 SCV000580990 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence

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.