Variant · Snv

VHL S65L (c.194C>T)

CI-VAR-00004095Explore in graph →NP_000542.1:p.Ser65LeuNM_000551.3:c.194C>TClinVar 182975 CIViC 1788 rs5030826

Curated evidence

Evidence by cancer (23 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–23 of 23 evidence items across 3 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Clear Cell Renal Cell Carcinoma1
VHL S65L (c.194C>T)	(oncogenic)	Oncogenic	C	Supports Oncogenicity	1	accepted	EID6131 This study analyzed tumor and non-tumor kidney tissue from 195 unrelated patients with sporadic clear cell renal cell carcinoma (CCRCC) for a relationship between VHL variants in sporadic CCRCC and 'g… (full text at CIViC) PMID 11505222 · Gallou et al., 2001 · Open in CIViC	civic
Kidney Carcinoma1
VHL S65L (c.194C>T)	(oncogenic)	Oncogenic	C	Supports Oncogenicity	1	accepted	EID6890 Tumors from 110 patients with sporadic renal carcinoma were analyzed for VHL mutations and loss of heterozygosity. 56 of the 98 samples from sporadic, clear cell renal carcinoma patients were identifi… (full text at CIViC) PMID 7915601 ·

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
182975	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Cerebellar hemangioblastoma; Pancreatic cysts; Retinal capillary hemangioma; Spinal hemangioblastoma; Von Hippel-Lindau syndrome; Chuvash polycythemia; Hereditary cancer-predisposing syndrome	germline	4	Aug 23, 2024	clinvar

Von Hippel-Lindau Disease21unmapped disease
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	3	accepted	EID4959 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
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	3	accepted	EID5104 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
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	2	accepted	EID5159 Genotype-phenotype correlations of 573 VHL patients from 200 kindreds were analyzed. This missense mutation was found in 4 VHL families of 11 patients altogether. Ten had retinal hemangioblastomas, 4 … (full text at CIViC) PMID 17024664 · Ong et al., 2007 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	2	accepted	EID5287 Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found in 96 control cases. This missense mutation was found in a VHL type 2 patient (patient no. V209). PMID 9829912 · Olschwang et al., 1998 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	2	accepted	EID5499 A study of 34 Polish families revealed germline mutations in 30 families. Mutations were not detected in 4 probands fulfilling clinical criteria for von Hippel-Lindau disease (VHLD). This missense mut… (full text at CIViC) PMID 12114495 · Cybulski et al., 2002 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	3	accepted	EID5582 Thirty-five unrelated patients suspected of having von Hippel-Lindau disease were analyzed and 32 VHL gene variants were found in 35 patients. An association of clear cell renal carcinoma development … (full text at CIViC) PMID 14722919 · Ruiz-Llorente et al., 2004 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	2	accepted	EID6644 Thirty-two surgically resected HB specimens from 28 patients treated at the University of Tokyo Hospital between 1995 and 2012 were analyzed retrospectively. Of the 32 specimens, 11 were VHL-related H… (full text at CIViC) PMID 28379443 · Takayanagi et al., 2017 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Uncertain Significance	2	accepted	EID6662 This retrospective study of 52 Danish patients with genetically confirmed VHL mutations analyzed the results of each individual's VHL-related examinations and manifestations diagnosed up to the time o… (full text at CIViC) PMID 25834951 · Binderup et al., 2016 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Uncertain Significance	3	accepted	EID6710 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. These inidiviuals were part of 223 VHL … (full text at CIViC) PMID 26308528 · Krzystolik et al., 2016 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Uncertain Significance	2	accepted	EID6728 240 ccRCC specimens were genetically analyzed. 3 specimens (ccRCC-58, ccRCC-154, ccRCC-238) from 3 different patients were confirmed to carry the p.Ser65Leu; c.194C>T mutation. The mutation was found … (full text at CIViC) PMID 23797736 · Sato et al., 2013 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	3	accepted	EID6791 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
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Uncertain Significance	3	submitted	EID6859 Medical records of 26 patients with germline mutations of the VHL gene who had been diagnosed with VHL disease in Severance Hospital (Seoul, Republic of Korea) and Samsung Medical Center (Seoul, Repub… (full text at CIViC) PMID 25078357 · Hwang et al., 2014 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	3	submitted	EID8569 A case report describes a 64Y old Japanese woman with VHL and a germline mutation p.Ser65Leu in the VHL gene. She presented with cerebellar hemangioblastoma at 37Y, underwent treatment for renal cell … (full text at CIViC) PMID 25282218 · Ikeda et al., 2014 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	2	submitted	EID8795 Tissues embedded in paraffin blocks were collected from 203 cHAB patients operated in different Medical Centres in Poland. Eight of these harboured germline mutations in unrelated patients from distin… (full text at CIViC) PMID 20233476 · Cybulski et al., 2004 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	3	submitted	EID8875 A 44-year-old man presented with a generalized epileptic attack. Diagnostic workup revealed a cystic left cerebellar tumor, which on histologic examination proved to be a hemangioblastoma. Identificat… (full text at CIViC) PMID 15905696 · Gijtenbeek et al., 2005 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	2	submitted	EID8975 Venous blood was genotyped for germline VHL mutations in 183 individuals with VHL disease spanning 81 unrelated pedigrees. 124 of 183 patients had retinal capillary hemangiomas (retinal angiomas). The… (full text at CIViC) PMID 10088816 · Webster et al., 1999 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	3	submitted	EID9038 A 32-year old man was consulted at the Polish VHL Registry as a member of a family with suspected von Hippel-Lindau disease (VHL). He presented with endolymphatic sac tumour (19Y; 21Y); cerebral heman… (full text at CIViC) PMID 19353437 · Krzysztolik et al., 2009 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	3	submitted	EID9127 A case report of a female patient with cereballar hemangioblastoma at 23Y and endolympathic sac tumour repeating at 23Y and 25Y revealed a mutation c.194C>T in the VHL gene. The mutation was found in … (full text at CIViC) PMID 18423895 · Skalova et al., 2008 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	3	submitted	EID9482 A retrospective analysis of 164 patients waiting for surgery for hemangioblastomas at Freiburg University Medical Center, Freiburg, Germany was conducted. Bidirectional direct sequencing by use of an … (full text at CIViC) PMID 23407287 · Gläsker et al., 2013 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	N/A N/A	2	submitted	EID9896 A cohort of 141 patients with hemangioblastomas of the central nervous system was analyzed. 81 patients had germline mutations in the VHL gene, analyzed through peripheral blood by Southern blotting a… (full text at CIViC) PMID 10567493 · Gläsker et al., 1999 · Open in CIViC	civic
VHL S65L (c.194C>T)	(predisposing)	Predisposing	C	Supports Predisposition	3	submitted	EID10430 Molecular and clinical analysis of 126 French VHL families tested for renal involvement revealed 92 different mutations. 90 of these families had renal involvement. The p.S65L (c.194C>T) germline vari… (full text at CIViC) PMID 15300849 · Gallou et al., 2004 · Open in CIViC	civic

Von Hippel-Lindau Disease21unmapped disease

VHL S65L (c.194C>T)

(predisposing)

Predisposing

Supports Predisposition

accepted

EID4959

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