NM_000551.3(VHL):c.487C>T (p.Leu163Phe) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jul 12, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001553667.1

Allele description [Variation Report for NM_000551.3(VHL):c.487C>T (p.Leu163Phe)]

NM_000551.3(VHL):c.487C>T (p.Leu163Phe)

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_000551.3(VHL):c.487C>T (p.Leu163Phe)
HGVS:
  • NC_000003.12:g.10149810C>T
  • NG_008212.3:g.13176C>T
  • NG_046756.1:g.7572C>T
  • NM_000551.3:c.487C>T
  • NM_001354723.2:c.*41C>T
  • NM_198156.3:c.364C>T
  • NP_000542.1:p.Leu163Phe
  • NP_937799.1:p.Leu122Phe
  • LRG_322t1:c.487C>T
  • LRG_322:g.13176C>T
  • LRG_322p1:p.Leu163Phe
  • NC_000003.11:g.10191494C>T
Protein change:
L122F
Links:
dbSNP: rs1553620318
NCBI 1000 Genomes Browser:
rs1553620318
Molecular consequence:
  • NM_001354723.2:c.*41C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.487C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.364C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001774604Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 12, 2021)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

von Hippel-Lindau gene mutation in non-syndromic familial pheochromocytomas.

Tong AL, Zeng ZP, Li HZ, Yang D, Lu L, Li M, Zhou YR, Zhang J, Chen S, Liang W.

Ann N Y Acad Sci. 2006 Aug;1073:203-7.

PubMed [citation]
PMID:
17102088

Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma.

Pandit R, Khadilkar K, Sarathi V, Kasaliwal R, Goroshi M, Khare S, Nair S, Raghavan V, Dalvi A, Hira P, Fernandes G, Sathe P, Rojekar A, Malhotra G, Bakshi G, Prakash G, Bhansali A, Walia R, Kamalanathan S, Sahoo J, Desai A, Bhagwat N, et al.

Eur J Endocrinol. 2016 Oct;175(4):311-23. doi: 10.1530/EJE-16-0126. Erratum in: Eur J Endocrinol. 2016 Dec;175(6):X3.

PubMed [citation]
PMID:
27539324
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001774604.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: VHL c.487C>T (p.Leu163Phe) results in a non-conservative amino acid change located in the von Hippel-Lindau disease tumour suppressor, beta/alpha domain (IPR022772) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251440 control chromosomes (gnomAD). c.487C>T has been reported in the literature in individuals affected with pheochromocytoma or paraganglioma (e.g. Tong_2006, Pandit_2016, Goldstein_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Aug 11, 2021

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