NM_000551.4(VHL):c.355T>C (p.Phe119Leu) AND Von Hippel-Lindau syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 5, 2016
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:: RCV000588483.2

Allele description [Variation Report for NM_000551.4(VHL):c.355T>C (p.Phe119Leu)]

NM_000551.4(VHL):c.355T>C (p.Phe119Leu)

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.355T>C (p.Phe119Leu)

HGVS:

NC_000003.12:g.10146528T>C
NG_008212.3:g.9894T>C
NG_046756.1:g.4290T>C
NM_000551.4:c.355T>CMANE SELECT
NM_001354723.2:c.*18-3259T>C
NM_198156.3:c.341-3259T>C
NP_000542.1:p.Phe119Leu
NP_000542.1:p.Phe119Leu
LRG_322t1:c.355T>C
LRG_322:g.9894T>C
LRG_322p1:p.Phe119Leu
NC_000003.11:g.10188212T>C
NM_000551.3:c.355T>C

Protein change:

F119L

Links:

dbSNP: rs1553619948

NCBI 1000 Genomes Browser:

rs1553619948

Molecular consequence:

NM_001354723.2:c.*18-3259T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3259T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000551.4:c.355T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Von Hippel-Lindau syndrome (VHLS)
Synonyms:: VHL syndrome; Von Hippel-Lindau
Identifiers:: MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000697505	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 5, 2016)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19270817, 10340905, 25078357, 12510195, 16142346, 19336503 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697505

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 5, 2016)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Improved detection of germline mutations in Korean VHL patients by multiple ligation-dependent probe amplification analysis.

Cho HJ, Ki CS, Kim JW.

J Korean Med Sci. 2009 Feb;24(1):77-83. doi: 10.3346/jkms.2009.24.1.77. Epub 2009 Feb 28.

PubMed [citation]

PMID:: 19270817
PMCID:: PMC2650969

Trichloroethylene exposure and specific somatic mutations in patients with renal cell carcinoma.

Brauch H, Weirich G, Hornauer MA, Störkel S, Wöhl T, Brüning T.

J Natl Cancer Inst. 1999 May 19;91(10):854-61.

PubMed [citation]

PMID:: 10340905

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697505.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: The c.355T>C (F119L) in VHL is a missense variant involving a highly conserved nucleotide and 3/4 in silico tools predict this variant to be deleterious (no prediction for SIFT). The variant was not found in the general population but was reported in at least 3 VHL patients. Another variant, c.357C>G, leading to the same amino acid change (F119L) and c.356T>C (F119S) have been reported in multiple VHL pts, indicating that this codon is a mutation hotspot. Additionally this variant has been identified as a somatic mutation in multiple renal cell carcinomas. Taken together, this is a disease variant and was classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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