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NM_000551.4(VHL):c.492G>T (p.Gln164His) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 30, 2023
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:
RCV003302779.2

Allele description [Variation Report for NM_000551.4(VHL):c.492G>T (p.Gln164His)]

NM_000551.4(VHL):c.492G>T (p.Gln164His)

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.492G>T (p.Gln164His)
HGVS:
  • NC_000003.12:g.10149815G>T
  • NG_008212.3:g.13181G>T
  • NG_046756.1:g.7577G>T
  • NM_000551.4:c.492G>TMANE SELECT
  • NM_001354723.2:c.*46G>T
  • NM_198156.3:c.369G>T
  • NP_000542.1:p.Gln164His
  • NP_000542.1:p.Gln164His
  • NP_937799.1:p.Gln123His
  • LRG_322t1:c.492G>T
  • LRG_322:g.13181G>T
  • LRG_322p1:p.Gln164His
  • NC_000003.11:g.10191499G>T
  • NM_000551.3:c.492G>T
Protein change:
Q123H
Links:
dbSNP: rs1352275281
NCBI 1000 Genomes Browser:
rs1352275281
Molecular consequence:
  • NM_001354723.2:c.*46G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.492G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.369G>T - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004000758Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(May 30, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.

Lenglet M, Robriquet F, Schwarz K, Camps C, Couturier A, Hoogewijs D, Buffet A, Knight SJL, Gad S, Couvé S, Chesnel F, Pacault M, Lindenbaum P, Job S, Dumont S, Besnard T, Cornec M, Dreau H, Pentony M, Kvikstad E, Deveaux S, Burnichon N, et al.

Blood. 2018 Aug 2;132(5):469-483. doi: 10.1182/blood-2018-03-838235. Epub 2018 Jun 11.

PubMed [citation]
PMID:
29891534

Details of each submission

From Ambry Genetics, SCV004000758.2

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

Description

The p.Q164H variant (also known as c.492G>T), located in coding exon 3 of the VHL gene, results from a G to T substitution at nucleotide position 492. The glutamine at codon 164 is replaced by histidine, an amino acid with highly similar properties. This alteration was identified with c.340+574A>T in an individual with splenomegaly (Lenglet M et al. Blood, 2018 Aug;132:469-483). p.Q164H has also been identified in multiple individuals with paraganglioma and/or pheochromocytoma (Bauters C et al. J. Med. Genet. 2003 Jun;40:e75; Meyer-Rochow GY et al. J. Surg. Res. 2009 Nov;157:55-62; Buffet A et al. Horm. Metab. Res. 2012 May;44:359-66; McInerney-Leo AM et al. Clin. Endocrinol. (Oxf) 2014 Jan;80:25-33). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024