NM_000179.3(MSH6):c.931_932insT (p.Lys311fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 5, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003595035.2

Allele description [Variation Report for NM_000179.3(MSH6):c.931_932insT (p.Lys311fs)]

NM_000179.3(MSH6):c.931_932insT (p.Lys311fs)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.931_932insT (p.Lys311fs)

HGVS:

NC_000002.12:g.47798914_47798915insT
NG_007111.1:g.20768_20769insT
NM_000179.3:c.931_932insTMANE SELECT
NM_001281492.2:c.541_542insT
NM_001281493.2:c.25_26insT
NM_001281494.2:c.25_26insT
NM_001406795.1:c.1027_1028insT
NM_001406796.1:c.931_932insT
NM_001406797.1:c.634_635insT
NM_001406798.1:c.931_932insT
NM_001406799.1:c.406_407insT
NM_001406800.1:c.931_932insT
NM_001406801.1:c.634_635insT
NM_001406802.1:c.1027_1028insT
NM_001406803.1:c.931_932insT
NM_001406804.1:c.853_854insT
NM_001406805.1:c.634_635insT
NM_001406806.1:c.406_407insT
NM_001406807.1:c.406_407insT
NM_001406808.1:c.931_932insT
NM_001406809.1:c.931_932insT
NM_001406811.1:c.25_26insT
NM_001406812.1:c.25_26insT
NM_001406813.1:c.937_938insT
NM_001406814.1:c.25_26insT
NM_001406815.1:c.25_26insT
NM_001406816.1:c.25_26insT
NM_001406817.1:c.931_932insT
NM_001406818.1:c.634_635insT
NM_001406819.1:c.634_635insT
NM_001406820.1:c.634_635insT
NM_001406821.1:c.634_635insT
NM_001406822.1:c.634_635insT
NM_001406823.1:c.25_26insT
NM_001406824.1:c.634_635insT
NM_001406825.1:c.634_635insT
NM_001406826.1:c.763_764insT
NM_001406827.1:c.634_635insT
NM_001406828.1:c.634_635insT
NM_001406829.1:c.25_26insT
NM_001406830.1:c.634_635insT
NM_001407362.1:c.628-1752_628-1751insT
NP_000170.1:p.Lys311Ilefs
NP_000170.1:p.Lys311fs
NP_001268421.1:p.Lys181fs
NP_001268422.1:p.Lys9fs
NP_001268423.1:p.Lys9fs
NP_001393724.1:p.Lys343fs
NP_001393725.1:p.Lys311fs
NP_001393726.1:p.Lys212fs
NP_001393727.1:p.Lys311fs
NP_001393728.1:p.Lys136fs
NP_001393729.1:p.Lys311fs
NP_001393730.1:p.Lys212fs
NP_001393731.1:p.Lys343fs
NP_001393732.1:p.Lys311fs
NP_001393733.1:p.Lys285fs
NP_001393734.1:p.Lys212fs
NP_001393735.1:p.Lys136fs
NP_001393736.1:p.Lys136fs
NP_001393737.1:p.Lys311fs
NP_001393738.1:p.Lys311fs
NP_001393740.1:p.Lys9fs
NP_001393741.1:p.Lys9fs
NP_001393742.1:p.Lys313fs
NP_001393743.1:p.Lys9fs
NP_001393744.1:p.Lys9fs
NP_001393745.1:p.Lys9fs
NP_001393746.1:p.Lys311fs
NP_001393747.1:p.Lys212fs
NP_001393748.1:p.Lys212fs
NP_001393749.1:p.Lys212fs
NP_001393750.1:p.Lys212fs
NP_001393751.1:p.Lys212fs
NP_001393752.1:p.Lys9fs
NP_001393753.1:p.Lys212fs
NP_001393754.1:p.Lys212fs
NP_001393755.1:p.Lys255fs
NP_001393756.1:p.Lys212fs
NP_001393757.1:p.Lys212fs
NP_001393758.1:p.Lys9fs
NP_001393759.1:p.Lys212fs
LRG_219t1:c.931_932insT
LRG_219:g.20768_20769insT
LRG_219p1:p.Lys311Ilefs
NC_000002.11:g.48026053_48026054insT
NM_000179.2:c.931_932insT
NR_176257.1:n.1020_1021insT
NR_176258.1:n.1020_1021insT
NR_176259.1:n.1020_1021insT
NR_176261.1:n.1020_1021insT

Protein change:

K136fs

Molecular consequence:

NM_000179.3:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.541_542insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406795.1:c.1027_1028insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406796.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406797.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406798.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406799.1:c.406_407insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406800.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406801.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406802.1:c.1027_1028insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406803.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406804.1:c.853_854insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406805.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406806.1:c.406_407insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406807.1:c.406_407insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406808.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406809.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406811.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406812.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406813.1:c.937_938insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406814.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406815.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406816.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406817.1:c.931_932insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406818.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406819.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406820.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406821.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406822.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406823.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406824.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406825.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406826.1:c.763_764insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406827.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406828.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406829.1:c.25_26insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406830.1:c.634_635insT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407362.1:c.628-1752_628-1751insT - intron variant - [Sequence Ontology: SO:0001627]
NR_176257.1:n.1020_1021insT - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176258.1:n.1020_1021insT - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176259.1:n.1020_1021insT - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176261.1:n.1020_1021insT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004261827	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18269114, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004261827

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 5, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004261827.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Lys311Ilefs*6) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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