NM_000179.3(MSH6):c.1474A>G (p.Met492Val) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Nov 30, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000212649.5

Allele description [Variation Report for NM_000179.3(MSH6):c.1474A>G (p.Met492Val)]

NM_000179.3(MSH6):c.1474A>G (p.Met492Val)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.1474A>G (p.Met492Val)
Other names:
p.M492V:ATG>GTG
HGVS:
  • NC_000002.12:g.47799457A>G
  • NG_007111.1:g.21311A>G
  • NM_000179.2:c.1474A>G
  • NM_000179.3:c.1474A>GMANE SELECT
  • NM_001281492.1:c.1084A>G
  • NM_001281493.1:c.568A>G
  • NM_001281494.1:c.568A>G
  • NP_000170.1:p.Met492Val
  • NP_000170.1:p.Met492Val
  • NP_001268421.1:p.Met362Val
  • NP_001268422.1:p.Met190Val
  • NP_001268423.1:p.Met190Val
  • LRG_219t1:c.1474A>G
  • LRG_219:g.21311A>G
  • LRG_219p1:p.Met492Val
  • NC_000002.11:g.48026596A>G
  • P52701:p.Met492Val
  • p.M492V
Protein change:
M190V
Links:
UniProtKB: P52701#VAR_042275; dbSNP: rs61754783
NCBI 1000 Genomes Browser:
rs61754783
Molecular consequence:
  • NM_000179.2:c.1474A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000179.3:c.1474A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.1:c.1084A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.1:c.568A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.1:c.568A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000712331Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Nov 30, 2016)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

MSH6 mutations are frequent in hereditary nonpolyposis colorectal cancer families with normal pMSH6 expression as detected by immunohistochemistry.

Okkels H, Lindorff-Larsen K, Thorlasius-Ussing O, Vyberg M, Lindebjerg J, Sunde L, Bernstein I, Klarskov L, Holck S, Krarup HB.

Appl Immunohistochem Mol Morphol. 2012 Oct;20(5):470-7. doi: 10.1097/PAI.0b013e318249739b.

PubMed [citation]
PMID:
22495361

Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population.

Nilbert M, Wikman FP, Hansen TV, Krarup HB, Orntoft TF, Nielsen FC, Sunde L, Gerdes AM, Cruger D, Timshel S, Bisgaard ML, Bernstein I, Okkels H.

Fam Cancer. 2009;8(1):75-83. doi: 10.1007/s10689-008-9199-3. Epub 2008 Jun 20.

PubMed [citation]
PMID:
18566915
See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000712331.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (6)

Description

The p.Met492Val variant in MSH6 has been reported in 4 individuals with Lynch sy ndrome-related cancers (Wagner 2003, Okkels 2012, Pal 2012). In vitro functional studies provide some evidence that the p.Met492Val variant may not impact prote in function (Drost 2012). However, these types of assays may not accurately repr esent biological function. This variant has been identified in 3/6610 Finnish ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs61754783). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In addit ion, this variant was classified as a Variant of Uncertain Significance on Sep 5 , 2013 by the ClinGen-approved InSiGHT expert panel (ClinVar SCV000107859.2). In summary, the clinical significance of the p.Met492Val variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jul 7, 2021

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