NM_000551.4(VHL):c.473T>C (p.Leu158Pro) AND Von Hippel-Lindau syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 4, 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:: RCV000208846.1

Allele description [Variation Report for NM_000551.4(VHL):c.473T>C (p.Leu158Pro)]

NM_000551.4(VHL):c.473T>C (p.Leu158Pro)

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.473T>C (p.Leu158Pro)

Other names:

p.L158P:CTG>CCG

HGVS:

NC_000003.12:g.10149796T>C
NG_008212.3:g.13162T>C
NG_046756.1:g.7558T>C
NM_000551.4:c.473T>CMANE SELECT
NM_001354723.2:c.*27T>C
NM_198156.3:c.350T>C
NP_000542.1:p.Leu158Pro
NP_000542.1:p.Leu158Pro
NP_937799.1:p.Leu117Pro
LRG_322t1:c.473T>C
LRG_322:g.13162T>C
LRG_322p1:p.Leu158Pro
NC_000003.11:g.10191480T>C
NM_000551.3:c.473T>C
P40337:p.Leu158Pro
p.[Leu158Pro]

Protein change:

L117P

Links:

UniProtKB: P40337#VAR_005748; dbSNP: rs121913346

NCBI 1000 Genomes Browser:

rs121913346

Molecular consequence:

NM_001354723.2:c.*27T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.473T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.350T>C - 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
SCV000264754	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	no assertion criteria provided	Pathogenic (Feb 26, 2016)	germline	clinical testing
SCV000697519	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 4, 2016)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19602254, 10563480, 8825919, 7977367, 9829912, 7728151 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000264754

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

no assertion criteria provided

Pathogenic
(Feb 26, 2016)

germline

clinical testing

SCV000697519

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 4, 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	yes	11	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Differences in regulation of tight junctions and cell morphology between VHL mutations from disease subtypes.

Bangiyeva V, Rosenbloom A, Alexander AE, Isanova B, Popko T, Schoenfeld AR.

BMC Cancer. 2009 Jul 14;9:229. doi: 10.1186/1471-2407-9-229.

PubMed [citation]

PMID:: 19602254
PMCID:: PMC2722669

Detection of a novel germline mutation in the von Hippel-Lindau tumour-suppressor gene by fluorescence-labelled base excision sequence scanning (F-BESS).

Brieger J, Weidt EJ, Gansen K, Decker HJ.

Clin Genet. 1999 Sep;56(3):210-5.

PubMed [citation]

PMID:: 10563480

See all PubMed Citations (6)

Details of each submission

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000264754.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	11	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		11	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697519.1

#	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.473T>C variant affects a conserved nucleotide, resulting in amino acid change from Leu to Pro. 4/4 in-silico tools predict damaging outcome for this variant. This variant has been reported in at least 8 VHL patients and not found in 120292 control chromosomes. In addition, one clinical laboratory classified this variant as pathogenic. Taken together, this variant 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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