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NM_000551.4(VHL):c.533T>C (p.Leu178Pro) AND Von Hippel-Lindau syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 2, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000767287.3

Allele description [Variation Report for NM_000551.4(VHL):c.533T>C (p.Leu178Pro)]

NM_000551.4(VHL):c.533T>C (p.Leu178Pro)

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.533T>C (p.Leu178Pro)
HGVS:
  • NC_000003.12:g.10149856T>C
  • NG_008212.3:g.13222T>C
  • NG_046756.1:g.7618T>C
  • NM_000551.4:c.533T>CMANE SELECT
  • NM_001354723.2:c.*87T>C
  • NM_198156.3:c.410T>C
  • NP_000542.1:p.Leu178Pro
  • NP_000542.1:p.Leu178Pro
  • NP_937799.1:p.Leu137Pro
  • LRG_322t1:c.533T>C
  • LRG_322:g.13222T>C
  • LRG_322p1:p.Leu178Pro
  • NC_000003.11:g.10191540T>C
  • NM_000551.3:c.533T>C
Protein change:
L137P
Links:
dbSNP: rs5030822
NCBI 1000 Genomes Browser:
rs5030822
Molecular consequence:
  • NM_001354723.2:c.*87T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.4:c.533T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.410T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000897845Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
criteria provided, single submitter

(DGD Variant Analysis Guidelines)		Pathogenic
(Aug 1, 2018) 		germlineclinical testing

Citation Link,

SCV005045786Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 2, 2024) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000897845.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV005045786.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The c.533T>C (p.Leu178Pro) variant in the VHL gene is located on the exon 3 and is predicted to replace leucine with proline at codon 178 (p.Leu178Pro). The variant has been reported in multiple unrelated individuals with von Hippel–Lindau disease and/or pheochromocytoma and segregate with disease (PMID: 31383958, 25867206, 19464396, 8956040, 9452106). An alternative variant disrupting the same amino acid (p.Leu178Arg) has been reported in individuals with Von Hippel-Lindau disease and interpreted as pathogenic (ClinVar ID: 625261). The variant is reported in ClinVar (ID: 428795). The variant is absent in the general population database (gnomAD). Computational prediction algorithms suggest a deleterious impact for this variant (REVEL score 0.951). Therefore, the c.533T>C (p.Leu178Pro) variant of VHL has been classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024