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NM_000551.4(VHL):c.452T>C (p.Ile151Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 17, 2019
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:
RCV000492569.3

Allele description [Variation Report for NM_000551.4(VHL):c.452T>C (p.Ile151Thr)]

NM_000551.4(VHL):c.452T>C (p.Ile151Thr)

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.452T>C (p.Ile151Thr)
HGVS:
  • NC_000003.12:g.10146625T>C
  • NG_008212.3:g.9991T>C
  • NG_046756.1:g.4387T>C
  • NM_000551.4:c.452T>CMANE SELECT
  • NM_001354723.2:c.*18-3162T>C
  • NM_198156.3:c.341-3162T>C
  • NP_000542.1:p.Ile151Thr
  • NP_000542.1:p.Ile151Thr
  • LRG_322t1:c.452T>C
  • LRG_322:g.9991T>C
  • LRG_322p1:p.Ile151Thr
  • NC_000003.11:g.10188309T>C
  • NM_000551.3:c.452T>C
Protein change:
I151T
Links:
dbSNP: rs869025655
NCBI 1000 Genomes Browser:
rs869025655
Molecular consequence:
  • NM_001354723.2:c.*18-3162T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3162T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.452T>C - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000580978Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(Jul 17, 2019)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

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

Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, van Velthoven V, Mulligan LM, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 2001 May;70(5):644-8.

PubMed [citation]
PMID:
11309459
PMCID:
PMC1737358
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000580978.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The p.I151T pathogenic mutation (also known as c.452T>C), located in coding exon 2 of the VHL gene, results from a T to C substitution at nucleotide position 452. The isoleucine at codon 151 is replaced by threonine, an amino acid with similar properties. The p.I151T alteration, also referred to as 665T>C in some literature, has been reported in individuals with a diagnosis or clinical features of VHL (Gläsker S et al. J. Neurol. Neurosurg. Psychiatr. 1999 Dec;67:758-62; Gläsker S et al. J. Neurol. Neurosurg. Psychiatry. 2001 May;70:644-8; Hes FJ et al. Clin. Genet. 2007 Aug;72:122-9; Ong KR et al. Hum. Mutat. 2007 Feb;28:143-9; Sriphrapradang C et al. Clin Med Insights Endocrinol Diabetes. 2017 Apr;10:1179551417705122; Krauss T et al. Endocr. Relat. Cancer. 2018 09;25:783-793; Ambry internal data). Based on internal structural analysis, this variant is more disruptive than known pathogenic variants (Testa A et al. J. Am. Chem. Soc., 2018 07;140:9299-9313). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 1, 2024