ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.353T>C (p.Leu118Pro) (rs5030830)

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
Ambry Genetics RCV000492175 SCV000580985 pathogenic Hereditary cancer-predisposing syndrome 2018-10-02 criteria provided, single submitter clinical testing The p.L118P pathogenic mutation (also known as c.353T>C), located in coding exon 2 of the VHL gene, results from a T to C substitution at nucleotide position 353. The leucine at codon 118 is replaced by proline, an amino acid with very few similar properties. This pathogenic mutation has been reported in numerous individuals diagnosed with VHL (Crossey PA et al. Hum Mol Genet. 1994 Aug;3(8):1303-8; Zbar B et al. Hum Mutat. 1996;8(4):348-57; Olschwang S et al. Hum. Mutat. 1998;12:424-30; Yoshida M et al. Jpn J Cancer Res. 2000 Feb;91(2):204-12; Gallou C et al. Hum Mutat. 2004 Sep;24(3):215-24; Benhammou JN et al. J. Urol. 2010 Nov;184:1855-9; Dandanell M et al. BMC Med Genet. 2012 Jul 16;13:54; Wong M et al. Chin J Cancer. 2016 Aug;35:79). Authors of another study concurred that missense mutations in the VHL gene are associated with a higher risk of pheochromocytomas, however they divided missense mutations into two subgroups:surface missense amino acid substitution mutations (SM) and deep missense mutations (DM). Missense mutations in the SM group were found to be at a significantly higher risk for pheochromocytomas than missense mutations in the DM group. The p.L118P variant was categorized as a DM due to its location in the protein core and the disruption of protein function (Ong KR et al. Hum. Mutat. 2007 Feb;28:143-9). Of note, this pathogenic mutation is also referred to as 566T>C in some literature. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000801496 SCV000941273 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 118 of the VHL protein (p.Leu118Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with von Hippel-Lindau (VHL) syndrome in families (PMID: 9829912, 25952756) and has been observed in several individuals affected with clinical features of VHL (PMID: 7987306, 8956040, 12202531, 17024664, 22799452, 27527340). This variant is also known as c.566T>C (p.Leu189Pro) in the literature. ClinVar contains an entry for this variant (Variation ID: 428807). This variant has been reported to affect VHL protein function (PMID: 14973063). For these reasons, this variant has been classified as Pathogenic.

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.