NM_000179.3(MSH6):c.3294C>A (p.Cys1098Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 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:: RCV003759104.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3294C>A (p.Cys1098Ter)]

NM_000179.3(MSH6):c.3294C>A (p.Cys1098Ter)

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.3294C>A (p.Cys1098Ter)

HGVS:

NC_000002.12:g.47803541C>A
NG_007111.1:g.25395C>A
NM_000179.3:c.3294C>AMANE SELECT
NM_001281492.2:c.2904C>A
NM_001281493.2:c.2388C>A
NM_001281494.2:c.2388C>A
NM_001406795.1:c.3390C>A
NM_001406796.1:c.3294C>A
NM_001406797.1:c.2997C>A
NM_001406799.1:c.2769C>A
NM_001406800.1:c.3294C>A
NM_001406801.1:c.2997C>A
NM_001406802.1:c.3390C>A
NM_001406803.1:c.2430C>A
NM_001406804.1:c.3216C>A
NM_001406805.1:c.2997C>A
NM_001406806.1:c.2769C>A
NM_001406807.1:c.2769C>A
NM_001406808.1:c.3294C>A
NM_001406809.1:c.3294C>A
NM_001406811.1:c.2388C>A
NM_001406812.1:c.2388C>A
NM_001406813.1:c.3300C>A
NM_001406814.1:c.2388C>A
NM_001406815.1:c.2388C>A
NM_001406816.1:c.2388C>A
NM_001406817.1:c.1728C>A
NM_001406818.1:c.2997C>A
NM_001406819.1:c.2997C>A
NM_001406820.1:c.2997C>A
NM_001406821.1:c.2997C>A
NM_001406822.1:c.2997C>A
NM_001406823.1:c.2388C>A
NM_001406824.1:c.2997C>A
NM_001406825.1:c.2997C>A
NM_001406826.1:c.3126C>A
NM_001406827.1:c.2997C>A
NM_001406828.1:c.2997C>A
NM_001406829.1:c.2388C>A
NM_001406830.1:c.2997C>A
NM_001406831.1:c.75C>A
NM_001406832.1:c.141C>A
NM_001407362.1:c.1239C>A
NP_000170.1:p.Cys1098Ter
NP_000170.1:p.Cys1098Ter
NP_001268421.1:p.Cys968Ter
NP_001268422.1:p.Cys796Ter
NP_001268423.1:p.Cys796Ter
NP_001393724.1:p.Cys1130Ter
NP_001393725.1:p.Cys1098Ter
NP_001393726.1:p.Cys999Ter
NP_001393728.1:p.Cys923Ter
NP_001393729.1:p.Cys1098Ter
NP_001393730.1:p.Cys999Ter
NP_001393731.1:p.Cys1130Ter
NP_001393732.1:p.Cys810Ter
NP_001393733.1:p.Cys1072Ter
NP_001393734.1:p.Cys999Ter
NP_001393735.1:p.Cys923Ter
NP_001393736.1:p.Cys923Ter
NP_001393737.1:p.Cys1098Ter
NP_001393738.1:p.Cys1098Ter
NP_001393740.1:p.Cys796Ter
NP_001393741.1:p.Cys796Ter
NP_001393742.1:p.Cys1100Ter
NP_001393743.1:p.Cys796Ter
NP_001393744.1:p.Cys796Ter
NP_001393745.1:p.Cys796Ter
NP_001393746.1:p.Cys576Ter
NP_001393747.1:p.Cys999Ter
NP_001393748.1:p.Cys999Ter
NP_001393749.1:p.Cys999Ter
NP_001393750.1:p.Cys999Ter
NP_001393751.1:p.Cys999Ter
NP_001393752.1:p.Cys796Ter
NP_001393753.1:p.Cys999Ter
NP_001393754.1:p.Cys999Ter
NP_001393755.1:p.Cys1042Ter
NP_001393756.1:p.Cys999Ter
NP_001393757.1:p.Cys999Ter
NP_001393758.1:p.Cys796Ter
NP_001393759.1:p.Cys999Ter
NP_001393760.1:p.Cys25Ter
NP_001393761.1:p.Cys47Ter
NP_001394291.1:p.Cys413Ter
LRG_219t1:c.3294C>A
LRG_219:g.25395C>A
LRG_219p1:p.Cys1098Ter
NC_000002.11:g.48030680C>A
NM_000179.2:c.3294C>A
NR_176256.1:n.2224C>A
NR_176257.1:n.3555C>A
NR_176258.1:n.3484C>A
NR_176259.1:n.3383C>A
NR_176260.1:n.1328C>A
NR_176261.1:n.3383C>A

Protein change:

C1042*

Molecular consequence:

NM_000179.3:c.3294C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.2904C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281493.2:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001281494.2:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406795.1:c.3390C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406796.1:c.3294C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406797.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406799.1:c.2769C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406800.1:c.3294C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406801.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406802.1:c.3390C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406803.1:c.2430C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406804.1:c.3216C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406805.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406806.1:c.2769C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406807.1:c.2769C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406808.1:c.3294C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406809.1:c.3294C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406811.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406812.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406813.1:c.3300C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406814.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406815.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406816.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406817.1:c.1728C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406818.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406819.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406820.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406821.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406822.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406823.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406824.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406825.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406826.1:c.3126C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406827.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406828.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406829.1:c.2388C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406830.1:c.2997C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406831.1:c.75C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406832.1:c.141C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001407362.1:c.1239C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004509164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30521064, 18269114, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004509164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 3, 2023)

germline

clinical testing

PubMed (4)
[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

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

Jiang W, Cai MY, Li SY, Bei JX, Wang F, Hampel H, Ling YH, Frayling IM, Sinicrope FA, Rodriguez-Bigas MA, Dignam JJ, Kerr DJ, Rosell R, Mao M, Li JB, Guo YM, Wu XY, Kong LH, Tang JH, Wu XD, Li CF, Chen JR, et al.

Int J Cancer. 2019 May 1;144(9):2161-2168. doi: 10.1002/ijc.32044. Epub 2019 Jan 9.

PubMed [citation]

PMID:: 30521064

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004509164.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with MSH6-related conditions (PMID: 30521064). ClinVar contains an entry for this variant (Variation ID: 1729871). This sequence change creates a premature translational stop signal (p.Cys1098*) 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). 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: Oct 8, 2024

ClinVar

Relating variation to medicine