U.S. flag

An official website of the United States government

NM_000551.4(VHL):c.500G>A (p.Arg167Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 15, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000213850.6

Allele description [Variation Report for NM_000551.4(VHL):c.500G>A (p.Arg167Gln)]

NM_000551.4(VHL):c.500G>A (p.Arg167Gln)

Genes:
LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [Gene]
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_000551.4(VHL):c.500G>A (p.Arg167Gln)
Other names:
NM_000551.4(VHL):c.500G>A
HGVS:
  • NC_000003.12:g.10149823G>A
  • NG_008212.3:g.13189G>A
  • NG_046756.1:g.7585G>A
  • NM_000551.4:c.500G>AMANE SELECT
  • NM_001354723.2:c.*54G>A
  • NM_198156.3:c.377G>A
  • NP_000542.1:p.Arg167Gln
  • NP_000542.1:p.Arg167Gln
  • NP_937799.1:p.Arg126Gln
  • LRG_322t1:c.500G>A
  • LRG_322:g.13189G>A
  • LRG_322p1:p.Arg167Gln
  • NC_000003.11:g.10191507G>A
  • NM_000551.3:c.500G>A
  • P40337:p.Arg167Gln
  • c.583C>T
  • p.[Arg167Gln]
Protein change:
R126Q; ARG167GLN
Links:
UniProtKB: P40337#VAR_005761; OMIM: 608537.0005; dbSNP: rs5030821
NCBI 1000 Genomes Browser:
rs5030821
Molecular consequence:
  • NM_001354723.2:c.*54G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.500G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.377G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000273601Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 15, 2021) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62.

PubMed [citation]
PMID:
10567493
PMCID:
PMC1736691

Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene.

Cybulski C, Krzystolik K, Murgia A, Górski B, Debniak T, Jakubowska A, Martella M, Kurzawski G, Prost M, Kojder I, Limon J, Nowacki P, Sagan L, Białas B, Kałuza J, Zdunek M, Omulecka A, Jaskólski D, Kostyk E, Koraszewska-Matuszewska B, Haus O, Janiszewska H, et al.

J Med Genet. 2002 Jul;39(7):E38. No abstract available.

PubMed [citation]
PMID:
12114495
PMCID:
PMC1735187
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000273601.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.R167Q pathogenic mutation (also known as c.500G>A), located in coding exon 3 of the VHL gene, results from a G to A substitution at nucleotide position 500. The arginine at codon 167 is replaced by glutamine, an amino acid with highly similar properties. This mutation has been described in numerous VHL families from various ethnic backgrounds (Zbar B et al. Hum. Mutat. 1996;8:348-57; Gläsker S et al. J. Neurol. Neurosurg. Psychiatr. 1999 Dec;67:758-62; Zhou J et al. Pathol. Int. 2010 Jun;60:452-8; Lee JS et al. BMC Med. Genet. 2016 Jul;17:48; Wang X et al. Urology. 2014 Mar;83:675.e1-5; Pandit R et al. Eur. J. Endocrinol. 2016 Oct;175:311-23; Wong M et al. Chin J Cancer. 2016 Aug;35:79). Furthermore, substitutions at codon 167 impact a highly-conserved protein surface residue and have been reported to confer high pheochromocytoma risk (Crossey PA et al. Hum. Mol. Genet. 1994 Aug;3:1303-8; Cybulski C et al. J. Med. Genet. 2002 Jul;39:E38; Ong KR et al. Hum. Mutat. 2007 Feb;28:143-9). Of note, this mutation has also been reported in some literature as p.R238Q ( c.713G>A). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024