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

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 5, 2013
Accession:
VCV000089328.6
Variation ID:
89328
Description:
single nucleotide variant
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NM_000179.3(MSH6):c.2983G>T

Allele ID
94802
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p16.3
Genomic location
2: 47800966 (GRCh38) GRCh38 UCSC
2: 48028105 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.48028105G>T
NC_000002.12:g.47800966G>T
NM_000179.3:c.2983G>T MANE Select
... more HGVS
Protein change
E995*, E865*, E693*
Other names
-
Canonical SPDI
NC_000002.12:47800965:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA011274
dbSNP: rs63750258
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 reviewed by expert panel Sep 5, 2013 RCV000074793.2
Pathogenic 1 criteria provided, single submitter Aug 26, 2016 RCV000491673.1
Pathogenic 1 criteria provided, single submitter Oct 13, 2020 RCV001062414.2
Pathogenic 1 criteria provided, single submitter Sep 18, 2019 RCV001269505.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MSH6 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
5633 5667

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 05, 2013)
reviewed by expert panel
Method: research
Lynch Syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000108004.2
Submitted: (Dec 18, 2013)
Comment:
Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs
Evidence details
Comment:
Coding sequence variation resulting in a stop codon
Likely pathogenic
(Feb 14, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695835.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (8)
Comment:
Variant summary: The MSH6 c.2983G>T (p.Glu995X) variant results in a premature termination codon, predicted to cause a truncated or absent MSH6 protein due to nonsense … (more)
Pathogenic
(Aug 26, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000580375.4
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (3)
Comment:
The p.E995* pathogenic mutation (also known as c.2983G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at … (more)
Pathogenic
(Oct 13, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV001227212.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
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 … (more)
Pathogenic
(Sep 18, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001449540.1
Submitted: (Nov 26, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. Rossi BM BMC cancer 2017 PMID: 28874130
Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population. Castellsagué E Clinical genetics 2015 PMID: 25318681
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 Nature genetics 2014 PMID: 24362816
Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases. Lotsari JE Breast cancer research : BCR 2012 PMID: 22691310
Detection of genetic alterations in hereditary colorectal cancer screening. Pineda M Mutation research 2010 PMID: 19931546
Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. Gylling AH Carcinogenesis 2008 PMID: 18550572
Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts. Devlin LA The Ulster medical journal 2008 PMID: 18269114
Two Swedish founder MSH6 mutations, one nonsense and one missense, conferring high cumulative risk of Lynch syndrome. Cederquist K Clinical genetics 2005 PMID: 16283884
Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome? Ollikainen M Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005 PMID: 15837969
No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer. Vahteristo P Journal of medical genetics 2005 PMID: 15805151
p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. Vahteristo P Cancer research 2001 PMID: 11479205
http://www.insight-database.org/classifications/index.html?gene=MSH6&variant=c.2983G%3ET - - - -

Text-mined citations for rs63750258...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021