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NM_000551.4(VHL):c.251T>A (p.Val84Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 30, 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:
RCV002433040.2

Allele description [Variation Report for NM_000551.4(VHL):c.251T>A (p.Val84Glu)]

NM_000551.4(VHL):c.251T>A (p.Val84Glu)

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.251T>A (p.Val84Glu)
HGVS:
  • NC_000003.12:g.10142098T>A
  • NG_008212.3:g.5464T>A
  • NM_000551.4:c.251T>AMANE SELECT
  • NM_001354723.2:c.251T>A
  • NM_198156.3:c.251T>A
  • NP_000542.1:p.Val84Glu
  • NP_000542.1:p.Val84Glu
  • NP_001341652.1:p.Val84Glu
  • NP_937799.1:p.Val84Glu
  • LRG_322t1:c.251T>A
  • LRG_322:g.5464T>A
  • LRG_322p1:p.Val84Glu
  • NC_000003.11:g.10183782T>A
  • NM_000551.3:c.251T>A
  • NR_176335.1:n.321T>A
Protein change:
V84E
Molecular consequence:
  • NM_000551.4:c.251T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.251T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.251T>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002742576Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 30, 2021) 		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

Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance.

Razafinjatovo C, Bihr S, Mischo A, Vogl U, Schmidinger M, Moch H, Schraml P.

BMC Cancer. 2016 Aug 17;16:638. doi: 10.1186/s12885-016-2688-0.

PubMed [citation]
PMID:
27530247
PMCID:
PMC4987997

Details of each submission

From Ambry Genetics, SCV002742576.2

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

Description

The p.V84E variant (also known as c.251T>A), located in coding exon 1 of the VHL gene, results from a T to A substitution at nucleotide position 251. The valine at codon 84 is replaced by glutamic acid, an amino acid with dissimilar properties. Two other alterations at the same codon, p.V84M (c.250G>A) and p.V84L (c.250G>C), have been reported in multiple individuals with von Hippel-Lindau syndrome (VHL) type 2C and/or pheochromocytomas (Crossey PA et al. J. Med. Genet.1995 Nov; 32(11):885-6; Abbott MA et al. Am. J. Med. Genet. A 2006 Apr; 140(7):685-90; Stanojevic BR et al. Neoplasma. 2007;54(5):402-6; Vignjevic J et al. 2007; Leonardi E et al. Ann. Hum. Genet. 2011 Jul; 75(4):483-96). 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: May 1, 2024