NM_000179.3(MSH6):c.2983G>T AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Oct 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001062414.2

Allele description [Variation Report for NM_000179.3(MSH6):c.2983G>T]

NM_000179.3(MSH6):c.2983G>T

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.2983G>T
HGVS:
  • NC_000002.12:g.47800966G>T
  • NG_007111.1:g.22820G>T
  • NM_000179.2:c.2983G>T
  • NM_000179.3:c.2983G>TMANE SELECT
  • NM_001281492.1:c.2593G>T
  • NM_001281493.1:c.2077G>T
  • NM_001281494.1:c.2077G>T
  • NP_000170.1:p.Glu995Ter
  • NP_001268421.1:p.Glu865Ter
  • NP_001268422.1:p.Glu693Ter
  • NP_001268423.1:p.Glu693Ter
  • LRG_219t1:c.2983G>T
  • LRG_219:g.22820G>T
  • LRG_219p1:p.Glu995Ter
  • NC_000002.11:g.48028105G>T
Protein change:
E693*
Links:
dbSNP: rs63750258
NCBI 1000 Genomes Browser:
rs63750258
Molecular consequence:
  • NM_000179.2:c.2983G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.1:c.2593G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.1:c.2077G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.1:c.2077G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001227212Invitaecriteria provided, single submitter
Pathogenic
(Oct 13, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer.

Vahteristo P, Ojala S, Tamminen A, Tommiska J, Sammalkorpi H, Kiuru-Kuhlefelt S, Eerola H, Aaltonen LA, Aittomäki K, Nevanlinna H.

J Med Genet. 2005 Apr;42(4):e22.

PubMed [citation]
PMID:
15805151
PMCID:
PMC1736038

Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases.

Lotsari JE, Gylling A, Abdel-Rahman WM, Nieminen TT, Aittomäki K, Friman M, Pitkänen R, Aarnio M, Järvinen HJ, Mecklin JP, Kuopio T, Peltomäki P.

Breast Cancer Res. 2012 Jun 12;14(3):R90.

PubMed [citation]
PMID:
22691310
PMCID:
PMC3446353
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001227212.2

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

Description

This sequence change creates a premature translational stop signal (p.Glu995*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 15805151, 22691310, 28874130). ClinVar contains an entry for this variant (Variation ID: 89328). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 23, 2021

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