U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.3699_3702del (p.Lys1233fs) AND Lynch syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 5, 2013
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000030271.8

Allele description [Variation Report for NM_000179.3(MSH6):c.3699_3702del (p.Lys1233fs)]

NM_000179.3(MSH6):c.3699_3702del (p.Lys1233fs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3699_3702del (p.Lys1233fs)
HGVS:
  • NC_000002.12:g.47806256_47806259del
  • NG_007111.1:g.28110_28113del
  • NG_008397.1:g.104419_104422del
  • NM_000179.3:c.3699_3702delMANE SELECT
  • NM_001281492.2:c.3309_3312del
  • NM_001281493.2:c.2793_2796del
  • NM_001281494.2:c.2793_2796del
  • NP_000170.1:p.Lys1233fs
  • NP_001268421.1:p.Lys1103fs
  • NP_001268422.1:p.Lys931fs
  • NP_001268423.1:p.Lys931fs
  • LRG_219:g.28110_28113del
  • NC_000002.11:g.48033393_48033396del
  • NC_000002.11:g.48033395_48033398del
  • NM_000179.2:c.3699_3702delAGAA
  • NM_000179.3:c.3699_3702del
  • p.K1233NFS*6
  • p.Lys1233Asnfs*6
  • p.Lys1233AsnfsX6
Protein change:
K1103fs
Links:
dbSNP: rs193922343
NCBI 1000 Genomes Browser:
rs193922343
Molecular consequence:
  • NM_000179.3:c.3699_3702del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.3309_3312del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.2793_2796del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.2793_2796del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000108129International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
reviewed by expert panel

(Guidelines v1.9)
Pathogenic
(Sep 5, 2013)
germlineresearch

Citation Link,

SCV004835113All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Feb 5, 2024)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing, research

Citations

PubMed

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Devlin LA, Graham CA, Price JH, Morrison PJ.

Ulster Med J. 2008 Jan;77(1):25-30.

PubMed [citation]
PMID:
18269114
PMCID:
PMC2397009

Mutation spectrum in HNPCC in the Israeli population.

Goldberg Y, Porat RM, Kedar I, Shochat C, Sagi M, Eilat A, Mendelson S, Hamburger T, Nissan A, Hubert A, Kadouri L, Pikarski E, Lerer I, Abeliovich D, Bercovich D, Peretz T.

Fam Cancer. 2008;7(4):309-17. doi: 10.1007/s10689-008-9191-y. Epub 2008 Apr 4.

PubMed [citation]
PMID:
18389388
See all PubMed Citations (9)

Details of each submission

From International Society for Gastrointestinal Hereditary Tumours (InSiGHT), SCV000108129.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided

Description

Coding sequence variation resulting in a stop codon

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

From All of Us Research Program, National Institutes of Health, SCV004835113.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (9)

Description

The c.3699_3702del variant in the MSH6 gene is located on the exon 8 and is predicted to shift the reading frame such that it introduces a premature translation termination codon (p.Lys1233Asnfs*6), resulting in an absent or disrupted protein product. This variant has been reported in multiple unrelated individuals with Lynch syndrome-related cancer (PMID: 25430799, 18389388, 28514183, 24933100, 25980754). Loss-of-function variants of MSH6 are known to be pathogenic (PMID: 30376427, 18269114, 29345684). The variant is reported in ClinVar as pathogenic (ID: 36593) and reviewed by the expert panel. The variant is rare in general population according to gnomAD (1/251238 chromosomes). Therefore, the c.3699_3702del (p.Lys1233Asnfs*6) variant in the MSH6 gene has been classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Nov 24, 2024