NM_000179.3(MSH6):c.1977dup (p.Lys660Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 3, 2023
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:: RCV003759705.2

Allele description [Variation Report for NM_000179.3(MSH6):c.1977dup (p.Lys660Ter)]

NM_000179.3(MSH6):c.1977dup (p.Lys660Ter)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.1977dup (p.Lys660Ter)

HGVS:

NC_000002.12:g.47799960dup
NG_007111.1:g.21814dup
NM_000179.3:c.1977dupMANE SELECT
NM_001281492.2:c.1587dup
NM_001281493.2:c.1071dup
NM_001281494.2:c.1071dup
NM_001406795.1:c.2073dup
NM_001406796.1:c.1977dup
NM_001406797.1:c.1680dup
NM_001406798.1:c.1977dup
NM_001406799.1:c.1452dup
NM_001406800.1:c.1977dup
NM_001406801.1:c.1680dup
NM_001406802.1:c.2073dup
NM_001406803.1:c.1977dup
NM_001406804.1:c.1899dup
NM_001406805.1:c.1680dup
NM_001406806.1:c.1452dup
NM_001406807.1:c.1452dup
NM_001406808.1:c.1977dup
NM_001406809.1:c.1977dup
NM_001406811.1:c.1071dup
NM_001406812.1:c.1071dup
NM_001406813.1:c.1983dup
NM_001406814.1:c.1071dup
NM_001406815.1:c.1071dup
NM_001406816.1:c.1071dup
NM_001406818.1:c.1680dup
NM_001406819.1:c.1680dup
NM_001406820.1:c.1680dup
NM_001406821.1:c.1680dup
NM_001406822.1:c.1680dup
NM_001406823.1:c.1071dup
NM_001406824.1:c.1680dup
NM_001406825.1:c.1680dup
NM_001406826.1:c.1809dup
NM_001406827.1:c.1680dup
NM_001406828.1:c.1680dup
NM_001406829.1:c.1071dup
NM_001406830.1:c.1680dup
NP_000170.1:p.Lys660Ter
NP_000170.1:p.Lys660Terfs
NP_001268421.1:p.Lys530Ter
NP_001268422.1:p.Lys358Ter
NP_001268423.1:p.Lys358Ter
NP_001393724.1:p.Lys692Terfs
NP_001393725.1:p.Lys660Terfs
NP_001393726.1:p.Lys561Terfs
NP_001393727.1:p.Lys660Terfs
NP_001393728.1:p.Lys485Terfs
NP_001393729.1:p.Lys660Terfs
NP_001393730.1:p.Lys561Terfs
NP_001393731.1:p.Lys692Terfs
NP_001393732.1:p.Lys660Terfs
NP_001393733.1:p.Lys634Terfs
NP_001393734.1:p.Lys561Terfs
NP_001393735.1:p.Lys485Terfs
NP_001393736.1:p.Lys485Terfs
NP_001393737.1:p.Lys660Terfs
NP_001393738.1:p.Lys660Terfs
NP_001393740.1:p.Lys358Terfs
NP_001393741.1:p.Lys358Terfs
NP_001393742.1:p.Lys662Terfs
NP_001393743.1:p.Lys358Terfs
NP_001393744.1:p.Lys358Terfs
NP_001393745.1:p.Lys358Terfs
NP_001393747.1:p.Lys561Terfs
NP_001393748.1:p.Lys561Terfs
NP_001393749.1:p.Lys561Terfs
NP_001393750.1:p.Lys561Terfs
NP_001393751.1:p.Lys561Terfs
NP_001393752.1:p.Lys358Terfs
NP_001393753.1:p.Lys561Terfs
NP_001393754.1:p.Lys561Terfs
NP_001393755.1:p.Lys604Terfs
NP_001393756.1:p.Lys561Terfs
NP_001393757.1:p.Lys561Terfs
NP_001393758.1:p.Lys358Terfs
NP_001393759.1:p.Lys561Terfs
LRG_219t1:c.1977dup
LRG_219:g.21814dup
LRG_219p1:p.Lys660Terfs
NC_000002.11:g.48027097_48027098insT
NC_000002.11:g.48027099dup
NM_000179.2:c.1977dup
NM_000179.2:c.1977dupT
NR_176256.1:n.839dup
NR_176257.1:n.2066dup
NR_176258.1:n.2066dup
NR_176259.1:n.2066dup
NR_176261.1:n.2066dup

Protein change:

K358*

Molecular consequence:

NM_001406795.1:c.2073dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406796.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406797.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406798.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406799.1:c.1452dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406800.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406801.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406802.1:c.2073dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406803.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406804.1:c.1899dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406805.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406806.1:c.1452dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406807.1:c.1452dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406808.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406809.1:c.1977dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406811.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406812.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406813.1:c.1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406814.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406815.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406816.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406818.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406819.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406820.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406821.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406822.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406823.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406824.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406825.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406826.1:c.1809dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406827.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406828.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406829.1:c.1071dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406830.1:c.1680dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000179.3:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.1587dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001281493.2:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001281494.2:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406795.1:c.2073dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406796.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406797.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406798.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406799.1:c.1452dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406800.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406801.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406802.1:c.2073dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406803.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406804.1:c.1899dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406805.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406806.1:c.1452dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406807.1:c.1452dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406808.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406809.1:c.1977dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406811.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406812.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406813.1:c.1983dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406814.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406815.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406816.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406818.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406819.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406820.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406821.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406822.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406823.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406824.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406825.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406826.1:c.1809dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406827.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406828.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406829.1:c.1071dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001406830.1:c.1680dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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Mus musculus RIKEN cDNA 8430415E04 gene (8430415E04Rik), mRNA
Mus musculus RIKEN cDNA 8430415E04 gene (8430415E04Rik), mRNA
gi|30794169|ref|NM_028980.1|

Nucleotide
ilEnnEroa1 alternate haplotype
ilEnnEroa1 alternate haplotype
Ennomos erosarius (September thorn) genome assembly, ilEnnEroa1, alternate haplotype

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004424241	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 3, 2023)	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

SCV004424241

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 3, 2023)

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, SCV004424241.1

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1783732). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys660*) 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).

#	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

ClinVar

Relating variation to medicine