NM_000551.4(VHL):c.265C>T (p.Leu89Phe) AND Von Hippel-Lindau syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 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:: RCV004001694.2

Allele description [Variation Report for NM_000551.4(VHL):c.265C>T (p.Leu89Phe)]

NM_000551.4(VHL):c.265C>T (p.Leu89Phe)

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.265C>T (p.Leu89Phe)

HGVS:

NC_000003.12:g.10142112C>T
NG_008212.3:g.5478C>T
NM_000551.4:c.265C>TMANE SELECT
NM_001354723.2:c.265C>T
NM_198156.3:c.265C>T
NP_000542.1:p.Leu89Phe
NP_000542.1:p.Leu89Phe
NP_001341652.1:p.Leu89Phe
NP_937799.1:p.Leu89Phe
LRG_322t1:c.265C>T
LRG_322:g.5478C>T
LRG_322p1:p.Leu89Phe
NC_000003.11:g.10183796C>T
NM_000551.3:c.265C>T

Protein change:

L89F

Links:

dbSNP: rs1575922124

NCBI 1000 Genomes Browser:

rs1575922124

Molecular consequence:

NM_000551.4:c.265C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.265C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.265C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV004824078	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Nov 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18446368, 25563310, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004824078

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Nov 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Germline mutations in the von Hippel-Lindau disease (VHL) gene in mainland Chinese families.

Zhang J, Huang Y, Pan J, Liu D, Zhou L, Xue W, Chen Q, Dong B, Xuan H.

J Cancer Res Clin Oncol. 2008 Nov;134(11):1211-8. doi: 10.1007/s00432-008-0399-x. Epub 2008 Apr 30.

PubMed [citation]

PMID:: 18446368

Clinical and genetic investigation of a multi-generational Chinese family afflicted with Von Hippel-Lindau disease.

Zhang J, Ma J, Du X, Wu D, Ai H, Bai J, Dong S, Yang Q, Qu K, Lyu Y, Valenzuela RK, Liu C.

Chin Med J (Engl). 2015 Jan 5;128(1):32-8. doi: 10.4103/0366-6999.147802.

PubMed [citation]

PMID:: 25563310
PMCID:: PMC4837816

See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004824078.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces leucine with phenylalanine at codon 89 of the VHL protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a family affected with type 1 Von Hippel-Lindau syndrome (PMID: 18446368, 25563310). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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