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NM_000179.3(MSH6):c.194C>T (p.Ser65Leu)

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Interpretation:
Likely benign​

Review status:
reviewed by expert panel
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 5, 2013
Accession:
VCV000089234.8
Variation ID:
89234
Description:
single nucleotide variant
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NM_000179.3(MSH6):c.194C>T (p.Ser65Leu)

Allele ID
94708
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p16.3
Genomic location
2: 47783427 (GRCh38) GRCh38 UCSC
2: 48010566 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.12:g.47783427C>T
NG_007111.1:g.5281C>T
NM_000179.3:c.194C>T MANE Select NP_000170.1:p.Ser65Leu missense
... more HGVS
Protein change
S65L
Other names
p.S65L:TCA>TTA
Canonical SPDI
NC_000002.12:47783426:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00008
Links
ClinGen: CA009482
UniProtKB: P52701#VAR_038034
dbSNP: rs41294984
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 1 reviewed by expert panel Sep 5, 2013 RCV000074698.4
Uncertain significance 1 criteria provided, single submitter Aug 20, 2018 RCV000160709.3
Uncertain significance 1 criteria provided, single submitter Oct 20, 2020 RCV000524128.5
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Apr 28, 2020 RCV000568962.4
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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
5681 5715

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Sep 05, 2013)
reviewed by expert panel
Method: research
Lynch Syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107903.2
Submitted: (Dec 18, 2013)
Comment:
Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs
Evidence details
Comment:
Multifactorial likelihood analysis posterior probability 0.001-0.049
Uncertain significance
(Aug 20, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000211340.13
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MSH6 c.194C>T at the cDNA level, p.Ser65Leu (S65L) at the protein level, and results in the change of a Serine to … (more)
Uncertain significance
(Apr 28, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000669945.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.S65L variant (also known as c.194C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide … (more)
Uncertain significance
(Oct 20, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000166215.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces serine with leucine at codon 65 of the MSH6 protein (p.Ser65Leu). The serine residue is weakly conserved and there is a … (more)
Benign
(Jun 14, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000911820.1
Submitted: (Nov 06, 2018)
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
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. Bodian DL PloS one 2014 PMID: 24728327
CoDP: predicting the impact of unclassified genetic variants in MSH6 by the combination of different properties of the protein. Terui H Journal of biomedical science 2013 PMID: 23621914
Classification of mismatch repair gene missense variants with PON-MMR. Ali H Human mutation 2012 PMID: 22290698
Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. Barnetson RA Human mutation 2008 PMID: 18033691
http://www.insight-database.org/classifications/index.html?gene=MSH6&variant=c.194C%3ET - - - -

Text-mined citations for rs41294984...

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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 Nov 27, 2021