chr3:10149823:G>A Detail (hg38) (VHL, LOC107303340)

Information

Genome

Assembly Position
hg19 chr3:10,191,507-10,191,507 View the variant detail on this assembly version.
hg38 chr3:10,149,823-10,149,823

HGVS

Type Transcript Protein
RefSeq NM_000551.3:c.500G>A NP_000542.1:p.Arg167Gln
NM_198156.2:c.377G>A NP_937799.1:p.Arg126Gln
Ensemble ENST00000256474.3:c.500G>A ENST00000256474.3:p.Arg167Gln
Summary

MGeND

Clinical significance Pathogenic
Variant entry 28
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance Conflicting classifications of pathogenicity
Review star
Show details
Links
Type Database ID Link
Gene MIM 608537 OMIM
HGNC 12687 HGNC
Ensembl ENSG00000134086 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM17983 COSMIC
MONDO
Disease area statistics
MGeND
Clinical significance Last evaluated Condition Origin Submission ID Submitter Institute Citation Comment Image
Pathogenic other germline MGS000001
(TMGS000138) 		Kenjiro Kosaki Keio University
Pathogenic other phakomatoses, not elsewhere classified germline MGS000077
(TMGS000152) 		Kenji Tamura Kochi University
Pathogenic Von Hippel-Lindau Type 1 (pheochromocytoma) germline MGS000001
(TMGS000162) 		Kenjiro Kosaki Keio University
Pathogenic Von Hippel-Lindau Type 2 germline MGS000001
(TMGS000162) 		Kenjiro Kosaki Keio University
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2023-05-21 criteria provided, multiple submitters, no conflicts Von Hippel-Lindau syndrome germline Detail
Pathogenic 2021-07-15 criteria provided, single submitter Hereditary cancer-predisposing syndrome germline Detail
Conflicting interpretations of pathogenicity 2023-05-19 criteria provided, conflicting interpretations not provided germline Detail
Pathogenic 2016-10-11 criteria provided, single submitter not specified germline Detail
Pathogenic 2023-12-23 criteria provided, single submitter Von Hippel-Lindau syndrome,Chuvash polycythemia germline Detail
Pathogenic 2023-12-23 criteria provided, single submitter Von Hippel-Lindau syndrome,Chuvash polycythemia germline Detail
Pathogenic 2023-03-01 criteria provided, single submitter pheochromocytoma germline Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 3 7728151 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 4 9829911 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 3 9829912 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 2 8707293 Detail
adrenal gland pheochromocytoma C Predisposing Supports Uncertain Significance Rare Germline 3 12000816 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 2 20660572 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 2 20846682 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 2 12114495 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 3 12624160 Detail
von Hippel-Lindau disease C Diagnostic Supports Positive Rare Germline 3 29396065 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 3 24132471 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 2 26763786 Detail
von Hippel-Lindau disease C Predisposing Supports Uncertain Significance Rare Germline 3 25867206 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.658 Von Hippel-Lindau syndrome NA CLINVAR Detail
0.416 pheochromocytoma Almost one fourth of patients with apparently sporadic pheochromocytoma may be c... UNIPROT 12000816 Detail
0.658 Von Hippel-Lindau syndrome The group of susceptibility genes for pheochromocytoma that included the proto-o... UNIPROT 12000816 Detail
Annotation

Annotations

DescrptionSourceLinks
In a study of 114 unrelated VHL families, 85 germline mutations were found. VHL mutations were detec... CIViC Evidence Detail
Germline mutations were found in all 93 families that fulfilled clinical criteria of VHL disease. Mu... CIViC Evidence Detail
Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. No variants were found... CIViC Evidence Detail
Of 65 VHL families from central Europe, 53 were identified with germline mutations. This missense mu... CIViC Evidence Detail
Peripheral blood from unrelated patients with pheochromocytoma was tested for mutations of proto-onc... CIViC Evidence Detail
53 patients with a molecularly confirmed VHL mutation and a pancreatic neuroendocrine tumor were col... CIViC Evidence Detail
26 VHL patients from 18 families, who had undergone a partial adrenalectomy for pheochromocytoma wer... CIViC Evidence Detail
A study of 34 Polish families revealed germline mutations in 30 families. Mutations were not detecte... CIViC Evidence Detail
Germline mutations were found in 20 Brazilian, VHL probands and their families. This missense mutati... CIViC Evidence Detail
A case report of a 51Y male patient presenting with headaches and a family history of VHL disease re... CIViC Evidence Detail
Data was collected from 82 VHL mutation carriers in the Dutch VHL surveillance program. Eleven patie... CIViC Evidence Detail
A prospective study followed 128 participants affected by VHL syndrome for 12 years in Padova, Italy... CIViC Evidence Detail
Patients with ELSTs in the VHL registries of the participating centers in Europe were identified and... CIViC Evidence Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND Von Hippel-Lindau syndrome ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND Hereditary cancer-predisposing syndrome ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND not provided ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND not specified ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND multiple conditions ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND multiple conditions ClinVar Detail
NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND Pheochromocytoma ClinVar Detail
NA DisGeNET Detail
Almost one fourth of patients with apparently sporadic pheochromocytoma may be carriers of mutations... DisGeNET Detail
The group of susceptibility genes for pheochromocytoma that included the proto-oncogene RET (associa... DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs5030821 dbSNP
Genome
hg38
Position
chr3:10,149,823-10,149,823
Variant Type
snv
Reference Allele
G
Alternative Allele
A
Variant (CIViC) (CIViC Variant)
R167Q (c.500G>A)
Transcript 1 (CIViC Variant)
ENST00000256474.2
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/1739
Summary (CIViC Variant)
R167Q is the most common point mutation in hereditary Von Hippel-Lindau (VHL) disease and disrupts the VHL genes binding to elongin C reducing the levels of the VHL-elongin B-elongin C (VBC) E3 ligase complex and inhibiting the ability of VHL to regulate HIF2α. This partial function in turn leads to an increased risk of tumorgenesis. VHL derived clear cell renal cell carcinoma models however have shown the proteasome inhibitors bortezomib and carfilzomib can act to stabilize mutant VHL-R167Q leading to downregulation of HIF2α and suprressed tumorgenesis.
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