NM_000551.4(VHL):c.273C>A (p.Phe91Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 14, 2022
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:: RCV000464337.7

Allele description [Variation Report for NM_000551.4(VHL):c.273C>A (p.Phe91Leu)]

NM_000551.4(VHL):c.273C>A (p.Phe91Leu)

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.273C>A (p.Phe91Leu)

Other names:

NM_000551.4(VHL):c.273C>A; p.Phe91Leu

HGVS:

NC_000003.12:g.10142120C>A
NG_008212.3:g.5486C>A
NM_000551.4:c.273C>AMANE SELECT
NM_001354723.2:c.273C>A
NM_198156.3:c.273C>A
NP_000542.1:p.Phe91Leu
NP_000542.1:p.Phe91Leu
NP_001341652.1:p.Phe91Leu
NP_937799.1:p.Phe91Leu
LRG_322t1:c.273C>A
LRG_322:g.5486C>A
LRG_322p1:p.Phe91Leu
NC_000003.11:g.10183804C>A
NM_000551.3:c.273C>A

Protein change:

F91L

Links:

dbSNP: rs1060503563

NCBI 1000 Genomes Browser:

rs1060503563

Molecular consequence:

NM_000551.4:c.273C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.273C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.273C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Chuvash polycythemia
Synonyms:: POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:: MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000553407	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12202531, 31337753, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000553407

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 14, 2022)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Retinal hemangioblastoma in von Hippel-Lindau disease: a clinical and molecular study.

Dollfus H, Massin P, Taupin P, Nemeth C, Amara S, Giraud S, Béroud C, Dureau P, Gaudric A, Landais P, Richard S.

Invest Ophthalmol Vis Sci. 2002 Sep;43(9):3067-74.

PubMed [citation]

PMID:: 12202531

Evolution of metazoan oxygen-sensing involved a conserved divergence of VHL affinity for HIF1α and HIF2α.

Tarade D, Lee JE, Ohh M.

Nat Commun. 2019 Jul 23;10(1):3293. doi: 10.1038/s41467-019-11149-1.

PubMed [citation]

PMID:: 31337753
PMCID:: PMC6650433

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000553407.5

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

Description

Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function. ClinVar contains an entry for this variant (Variation ID: 411978). This missense change has been observed in individual(s) with retinal hemangioblastoma (PMID: 12202531). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 91 of the VHL protein (p.Phe91Leu). Experimental studies have shown that this missense change affects VHL function (PMID: 31337753). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.

#	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

ClinVar

Relating variation to medicine