ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.223A>C (p.Ile75Leu)

dbSNP: rs1060503554
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466296 SCV000553386 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2016-10-22 criteria provided, single submitter clinical testing In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a VHL-related disease. This sequence change replaces isoleucine with leucine at codon 75 of the VHL protein (p.Ile75Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine.
Ambry Genetics RCV000571595 SCV000675817 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-13 criteria provided, single submitter clinical testing The p.I75L variant (also known as c.223A>C), located in coding exon 1 of the VHL gene, results from an A to C substitution at nucleotide position 223. The isoleucine at codon 75 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6401 samples (12802 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 12000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration 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.