NM_000551.4(VHL):c.439A>G (p.Ile147Val) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Oct 19, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000657081.1

Allele description [Variation Report for NM_000551.4(VHL):c.439A>G (p.Ile147Val)]

NM_000551.4(VHL):c.439A>G (p.Ile147Val)

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.439A>G (p.Ile147Val)
HGVS:
  • NC_000003.12:g.10146612A>G
  • NG_008212.3:g.9978A>G
  • NG_046756.1:g.4374A>G
  • NM_000551.3:c.439A>G
  • NM_000551.4:c.439A>GMANE SELECT
  • NM_001354723.2:c.*18-3175A>G
  • NM_198156.3:c.341-3175A>G
  • NP_000542.1:p.Ile147Val
  • NP_000542.1:p.Ile147Val
  • LRG_322t1:c.439A>G
  • LRG_322:g.9978A>G
  • LRG_322p1:p.Ile147Val
  • NC_000003.11:g.10188296A>G
  • NM_000551.2:c.439A>G
Protein change:
I147V
Links:
dbSNP: rs1057517560
NCBI 1000 Genomes Browser:
rs1057517560
Molecular consequence:
  • NM_001354723.2:c.*18-3175A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3175A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.3:c.439A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000551.4:c.439A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000568592GeneDxcriteria provided, single submitter
Uncertain significance
(Oct 19, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000568592.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted VHL c.439A>G at the cDNA level, p.Ile147Val (I147V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). This variant was observed in at least one individual with bilateral renal carcinomas (Petersson 2011). VHL Ile147Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Isoleucine and Valine share similar properties, this is considered a conservative amino acid substitution. VHL Ile147Val occurs at a position that is not conserved and is located in the beta-domain and the region involved in binding to the CCT complex (UniProt, Yuen 2009). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether VHL Ile147Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: Nov 27, 2021

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