ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.224T>G (p.Ile75Ser) (rs1064794271)

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
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000767237 SCV000897780 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
GeneDx RCV000479941 SCV000568590 uncertain significance not provided 2016-08-03 criteria provided, single submitter clinical testing This variant is denoted VHL c.224T>G at the cDNA level, p.Ile75Ser (I75S) at the protein level, and results in the change of an Isoleucine to a Serine (ATC>AGC). This variant was observed in at least one individual suspected of having von Hippel-Lindau (VHL) with no additional clinical information provided (Ong 2007). VHL Ile75Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Isoleucine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. VHL Ile75Ser occurs at a position that is conserved in mammals and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Splicing models suggest that a cryptic splice donor site is created upstream of the natural splice donor site; however the natural splice donor site is not predicted to be changed. In the absence of RNA or functional studies, the actual effect of this variant on splicing is unknown. Based on currently available evidence, it is unclear whether VHL Ile75Ser is a pathogenic or benign variant. We consider it to be 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.