NM_000551.4(VHL):c.631A>C (p.Met211Leu) AND not specified

Clinical significance:Uncertain significance (Last evaluated: May 15, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000161101.5

Allele description [Variation Report for NM_000551.4(VHL):c.631A>C (p.Met211Leu)]

NM_000551.4(VHL):c.631A>C (p.Met211Leu)

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.631A>C (p.Met211Leu)
Other names:
p.M211L:ATG>CTG
HGVS:
  • NC_000003.12:g.10149954A>C
  • NG_008212.3:g.13320A>C
  • NG_046756.1:g.7716A>C
  • NM_000551.3:c.631A>C
  • NM_000551.4:c.631A>CMANE SELECT
  • NM_001354723.2:c.*185A>C
  • NM_198156.3:c.508A>C
  • NP_000542.1:p.Met211Leu
  • NP_000542.1:p.Met211Leu
  • NP_937799.1:p.Met170Leu
  • LRG_322t1:c.631A>C
  • LRG_322:g.13320A>C
  • LRG_322p1:p.Met211Leu
  • NC_000003.11:g.10191638A>C
  • NC_000003.11:g.10191638A>C
Protein change:
M170L
Links:
dbSNP: rs200019083
NCBI 1000 Genomes Browser:
rs200019083
Molecular consequence:
  • NM_001354723.2:c.*185A>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.631A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000551.4:c.631A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.508A>C - 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
SCV000697528Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(May 15, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Next-generation sequencing in familial breast cancer patients from Lebanon.

Jalkh N, Chouery E, Haidar Z, Khater C, Atallah D, Ali H, Marafie MJ, Al-Mulla MR, Al-Mulla F, Megarbane A.

BMC Med Genomics. 2017 Feb 15;10(1):8. doi: 10.1186/s12920-017-0244-7.

PubMed [citation]
PMID:
28202063
PMCID:
PMC5312584

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697528.2

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

Description

Variant summary: VHL c.631A>C (p.Met211Leu) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.5e-05 in 276540 control chromosomes (gnomAD). The observed variant frequency is approximately 1.2 fold above the estimated maximal expected allele frequency for a pathogenic variant in VHL causing Von Hippel-Lindau Syndrome phenotype (2.1e-05), suggesting that the variant might be benign. The variant, c.631A>C, has been reported in the literature in individuals affected with Breast Cancer (Jalkh_2017). This report does not provide unequivocal conclusions about association of the variant with Von Hippel-Lindau Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2x likely benign, 1x uncertain significance). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Oct 25, 2021

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