NM_000551.4(VHL):c.290C>T (p.Pro97Leu) AND Von Hippel-Lindau syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV004011117.2

Allele description [Variation Report for NM_000551.4(VHL):c.290C>T (p.Pro97Leu)]

NM_000551.4(VHL):c.290C>T (p.Pro97Leu)

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.290C>T (p.Pro97Leu)

HGVS:

NC_000003.12:g.10142137C>T
NG_008212.3:g.5503C>T
NM_000551.4:c.290C>TMANE SELECT
NM_001354723.2:c.290C>T
NM_198156.3:c.290C>T
NP_000542.1:p.Pro97Leu
NP_001341652.1:p.Pro97Leu
NP_937799.1:p.Pro97Leu
LRG_322t1:c.290C>T
LRG_322:g.5503C>T
NC_000003.11:g.10183821C>T
NM_000551.3:c.290C>T

Protein change:

P97L

Links:

dbSNP: rs2125125249

NCBI 1000 Genomes Browser:

rs2125125249

Molecular consequence:

NM_000551.4:c.290C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.290C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.290C>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
SCV004830388	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15300849, 16314641, 19763184, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004830388

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 28, 2023)

germline

clinical testing

PubMed (4)
[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	1	not provided	not provided	108544	not provided	clinical 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

Genetic testing in pheochromocytoma or functional paraganglioma.

Amar L, Bertherat J, Baudin E, Ajzenberg C, Bressac-de Paillerets B, Chabre O, Chamontin B, Delemer B, Giraud S, Murat A, Niccoli-Sire P, Richard S, Rohmer V, Sadoul JL, Strompf L, Schlumberger M, Bertagna X, Plouin PF, Jeunemaitre X, Gimenez-Roqueplo AP.

J Clin Oncol. 2005 Dec 1;23(34):8812-8.

PubMed [citation]

PMID:: 16314641

See all PubMed Citations (4)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004830388.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces proline with leucine at codon 97 of the VHL protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least two families affected with VHL and in an individual affected with pheochromocytoma (PMID: 15300849, 16314641, 19763184). 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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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