Gene

VHL

von Hippel-Lindau tumor suppressor

Explore in graph →CI-GENE-00038379HGNC:12687 ENSG00000134086 NCBI 7428 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (2,994)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 551–600 of 2,994 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
VHL F136S (c.407T>C)15
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted

Cohorts

Alteration frequency by cohort (42)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

gdcObserved42 cohort rows · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Kidney Renal Clear Cell Carcinoma TCGA-KIRC	Clear Cell Renal Cell Carcinoma	Ssm

Literature

Linked publications (98)

25 per page, newest first.

pubmedPublishedShowing 76–98 of 98 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Genetic screening for von Hippel-Lindau gene mutations in non-syndromic pheochromocytoma: low prevalence and false-positives or misdiagnosis indicate a need for caution.
· Horm Metab Res · 2012 · PMID 22438210 · validated civic_curation pubmed
The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.
· J Neurol Neurosurg Psychiatry · 1999 · PMID 10567493 · validated civic_curation pubmed
Identification of a novel mutation (c279delC) and a polymorphism (c291C>G) in the von Hippel-Lindau gene in Italian patients.
· Hum Mutat · 2000 · PMID 10862095 · validated civic_curation pubmed
Clinical features of pancreatic involvement in von Hippel-Lindau disease: a retrospective study of 55 cases in a single center.
· Scand J Gastroenterol · 2015 · PMID 25562111

VHL F136V (c.406T>G)1
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID9193 A case report describes a 9-year-old boy with multifocal paraganglioma partially involving the right suprarenal gland, abdominal paraganglia, and the left para-aortal retropleural region and pheochrom… (full text at CIViC) PMID 12053037 · Tröbs et al., 2002 · Open in CIViC	civic

VHL F136V (c.406T>G)1

(predisposing)

Von Hippel-Lindau DiseaseUNRESOLVED

Predisposing

N/A N/A

submitted

EID9193

A case report describes a 9-year-old boy with multifocal paraganglioma partially involving the right suprarenal gland, abdominal paraganglia, and the left para-aortal retropleural region and pheochrom… (full text at CIViC)

PMID 12053037 · Tröbs et al., 2002 · Open in CIViC

VHL F76del (c.227_229del)26
(predisposing)	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	accepted	EID4919 This deletion mutation was found in two VHL type 1 families of 15 individuals altogether (Family IDs 2693 and 2956 in publication). Five of 7 individuals were identified with retinal hemangioblastomas… (full text at CIViC) PMID 7728151 · Chen et al., 1995 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	accepted	EID5682 This paper reports on 4 Chinese kindreds with VHL. The VHL gene was screened using direct DNA sequencing and MLPA in 44 volunteers among the 4 families. The above mutation was found in 1 kindred; 10 m… (full text at CIViC) PMID 23143947 · Chen et al., 2013 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	4	submitted	EID7752 Patients presenting with cerebellar hemangioblastomas at the Mexican National institute of Neurology and Neurosurgery to were prospectively enrolled alongside family members, resulting in 84 patients … (full text at CIViC) PMID 16572651 · Rasmussen et al., 2006 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5378 'Germline mutation analysis of 469 VHL families reveled 300 mutations. The most common germline mutations were identified between codons 75-82, between codons 157-189 (Elongin binding domain) and at t… (full text at CIViC) PMID 8956040 · Zbar et al., 1996 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5386 A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot an… (full text at CIViC) PMID 10761708 · Yoshida et al., 2000 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5421 20 individuals in 12 unrelated Brazilian families were referred for clinical suspicion of Von Hippel-Lindau disease. 16 of these individuals from 8 families fulfilled classical VHL diagnostic criteria… (full text at CIViC) PMID 20567917 · Gomy et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID5540 Germline mutations were found in 20 Brazilian, VHL probands and their families. This mutation was found in a VHL type 1 family of 5 affected individuals (VHL family 1). Four patients had hemangioblast… (full text at CIViC) PMID 12624160 · Rocha et al., 2003 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5596 64 VHL patients with renal involvement were analyzed. 61 of the 64 patients had a known germline mutation. The above mutation was identified in 4 patients. Clinical manifestations included renal cell … (full text at CIViC) PMID 22156657 · Jilg et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID5636 Tissue analysis from 61 VHL patients revealed 22 variants within VHL gene open reading frame. All mutations cluster to the 3’ end of the VHL gene open reading frame, implicating this region as importa… (full text at CIViC) PMID 7977367 · Whaley et al., 1994 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5641 An investigation of 94 VHL patients without large deletions for intragenic mutations revealed 40 different mutations in 55 unrelated individuals. In all patients with multiple affected family members … (full text at CIViC) PMID 7987306 · Crossey et al., 1994 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5650 Germline mutations were found in all 93 families that fulfilled clinical criteria of VHL disease. Mutations predicted to inactivate the VHL protein were associated with renal cell carcinoma and hemang… (full text at CIViC) PMID 9829911 · Stolle et al., 1998 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5744 Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed and confirmed that higher risk of pheochromocytoma is associated with missense mutations that result in substitution… (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5749 Between 1994 and 2001, the Dutch VHL working group conducted DNA analysis on 146 probands with VHL-associated manifestations. DNA of probands was extracted from peripheral blood samples. Exons 1, 2 an… (full text at CIViC) PMID 17661816 · Hes et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5750 This study reports 1,548 germline and somatic mutations from 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). This exon was detected in a VHL … (full text at CIViC) PMID 20151405 · Nordstrom-O'Brien et al., 2010 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID5766 Mutational analysis for 16 patients with clinically diagnosed VHL disease, revealed 12 germline mutations. This mutation was found in a 42-year-old VHL patient with hemangioblastomas of the central ne… (full text at CIViC) PMID 22357542 · Wu et al., 2012 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	rejected	EID6121 Molecular analysis of VHL gene in 146 probands, 103 with and 43 without a positive family history, resulted in the detection of 43 germline VHL mutations. Majority of mutations were found in patients … (full text at CIViC) PMID 17661816 · Hes et al., 2007 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6711 A retrospective study reviewed cases of 23 patients with advanced and complicated VHL eye disease who underwent pars plana vitrectomy in the years 1999 to 2012 that were a part of 223 VHL patients con… (full text at CIViC) PMID 26308528 · Krzystolik et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6712 A retrospective study reviewed cases of 23 patients with advanced and complicated VHL eye disease who underwent pars plana vitrectomy in the years 1999 to 2012 that were a part of 223 VHL patients con… (full text at CIViC) PMID 26308528 · Krzystolik et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6743 Direct sequencing and multiplex ligation dependent probe amplification were performed on thirteen unrelated subjects with VHL mutations. The clinical manifestations and family histories of the subject… (full text at CIViC) PMID 27439424 · Lee et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	submitted	EID6758 150 index patients with pheochromocytoma/paraganglioma were evaluated. Phenotypic data were collected and germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested. G… (full text at CIViC) PMID 27539324 · Pandit et al., 2016 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6784 Medical records of 31 genetically proven VHL patients with pheochromocytoma/paraganglioma were studied. A 29 year old Asian Indian male presented with unilateral pheochromocytoma, pancreatic cysts, an… (full text at CIViC) PMID 29124493 · Lomte et al., 2018 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6794 A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were… (full text at CIViC) PMID 28388566 · Peng et al., 2017 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	Supports Predisposition	3	accepted	EID6862 Medical records of 26 patients diagnosed with VHL disease in two Korean hospitals between 2003-2012 and harboring germline VHL mutations were retrospectively reviewed. One male patient diagnosed with … (full text at CIViC) PMID 25078357 · Hwang et al., 2014 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8138 33 patients diagnosed with VHL disease, according to (Maher et al. 1990), were tested for germline VHL mutations. Genetic testing was performed on high-molecular-weight DNA from peripheral blood using… (full text at CIViC) PMID 9106522 · Prowse et al., 1997 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8380 Of 31 Brazilian patients, one was found to harbour the c.227_229delTCT (p.Phe76del) mutation of the VHL gene. Genomic DNA was extracted and all VHL coding regions were analyzed by Sanger sequencing. M… (full text at CIViC) PMID 31528828 · Fagundes et al., 2019 · Open in CIViC	civic
〃	Von Hippel-Lindau DiseaseUNRESOLVED	Predisposing	C	N/A N/A	3	submitted	EID8430 Fourty-four of 389 patients with VHL (between 1988-1999) screened positive for PNETs either by pathologic analysis of tissue specimens or by characteristic radiographic appearance on CT and MRI. VHL g… (full text at CIViC) PMID 11114638 · Libutti et al., 2000 · Open in CIViC	civic