NM_000551.4(VHL):c.484T>C (p.Cys162Arg) AND Von Hippel-Lindau syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 1, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000587033.2

Allele description [Variation Report for NM_000551.4(VHL):c.484T>C (p.Cys162Arg)]

NM_000551.4(VHL):c.484T>C (p.Cys162Arg)

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.484T>C (p.Cys162Arg)
HGVS:
  • NC_000003.12:g.10149807T>C
  • NG_008212.3:g.13173T>C
  • NG_046756.1:g.7569T>C
  • NM_000551.3:c.484T>C
  • NM_000551.4:c.484T>CMANE SELECT
  • NM_001354723.2:c.*38T>C
  • NM_198156.3:c.361T>C
  • NP_000542.1:p.Cys162Arg
  • NP_000542.1:p.Cys162Arg
  • NP_937799.1:p.Cys121Arg
  • LRG_322t1:c.484T>C
  • LRG_322:g.13173T>C
  • LRG_322p1:p.Cys162Arg
  • NC_000003.11:g.10191491T>C
Protein change:
C121R
Links:
dbSNP: rs1553620313
NCBI 1000 Genomes Browser:
rs1553620313
Molecular consequence:
  • NM_001354723.2:c.*38T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000551.4:c.484T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697521Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Aug 31, 2016)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000897833Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
Pathogenic
(Aug 1, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Improved detection of germline mutations in Korean VHL patients by multiple ligation-dependent probe amplification analysis.

Cho HJ, Ki CS, Kim JW.

J Korean Med Sci. 2009 Feb;24(1):77-83. doi: 10.3346/jkms.2009.24.1.77. Epub 2009 Feb 28.

PubMed [citation]
PMID:
19270817
PMCID:
PMC2650969

VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma.

Lessi F, Mazzanti CM, Tomei S, Di Cristofano C, Minervini A, Menicagli M, Apollo A, Masieri L, Collecchi P, Minervini R, Carini M, Bevilacqua G.

Med Oncol. 2014 Mar;31(3):840. doi: 10.1007/s12032-014-0840-8. Epub 2014 Jan 21.

PubMed [citation]
PMID:
24446253
See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697521.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

Variant summary: The c.484C>T (p.Cys162Arg) in VHL gene is a missense change that involves a non-conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant of interest is located within the elongin binding domain, and mutations in this region have been found in multiple VHL patients. The variant is absent from the control population dataset of ExAC but has been reported in multiple affected individuals from VHL families and was proven to segregate with the disease. In addition, codon Cy162 appears to be a hotspot, since other alterations of this codon, p.C162W, p.C162Y and p.C162F, were found in multiple VHL pts. Taking together, the variant was classified as Pathogenic.

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

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000897833.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Oct 30, 2021

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