NM_000551.4(VHL):c.463G>T (p.Val155Leu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Likely pathogenic (Last evaluated: Mar 10, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001022829.1

Allele description [Variation Report for NM_000551.4(VHL):c.463G>T (p.Val155Leu)]

NM_000551.4(VHL):c.463G>T (p.Val155Leu)

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.463G>T (p.Val155Leu)
HGVS:
  • NC_000003.12:g.10146636G>T
  • NG_008212.3:g.10002G>T
  • NG_046756.1:g.4398G>T
  • NM_000551.4:c.463G>TMANE SELECT
  • NM_001354723.2:c.*18-3151G>T
  • NM_198156.3:c.341-3151G>T
  • NP_000542.1:p.Val155Leu
  • LRG_322t1:c.463G>T
  • LRG_322:g.10002G>T
  • NC_000003.11:g.10188320G>T
  • NM_000551.3:c.463G>T
Protein change:
V155L
Links:
dbSNP: rs869025659
NCBI 1000 Genomes Browser:
rs869025659
Molecular consequence:
  • NM_001354723.2:c.*18-3151G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3151G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.463G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001184608Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Mar 10, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

Gallou C, Chauveau D, Richard S, Joly D, Giraud S, Olschwang S, Martin N, Saquet C, Chrétien Y, Méjean A, Correas JM, Benoît G, Colombeau P, Grünfeld JP, Junien C, Béroud C.

Hum Mutat. 2004 Sep;24(3):215-24. Erratum in: Hum Mutat. 2004 Nov;24(5):435-6.

PubMed [citation]
PMID:
15300849

Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese VHL. Clinical Research Group for VHL in Japan.

[No authors listed]

Hum Mol Genet. 1995 Dec;4(12):2233-7.

PubMed [citation]
PMID:
8634692

Details of each submission

From Ambry Genetics, SCV001184608.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.463G>T variant (also known as p.V155L), located in coding exon 2 of the VHL gene, results from a G to T substitution at nucleotide position 463. This change occurs in the last base pair of coding exon 2, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Two other nucleotide substitutions at the same position, c.463G>C and c.463G>A (also designated 676G>A), have been detected in individuals diagnosed with VHL (Kondo K et al. Hum. Mol. Genet. 1995 Dec;4:2233-7; Gallou C et al. Hum. Mutat. 2004 Sep;24:215-24). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jan 9, 2021

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