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NM_000179.3(MSH6):c.1847C>G (p.Ser616Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(6)

Review status:
criteria provided, conflicting interpretations
Submissions:
7 (Most recent: Jun 15, 2021)
Last evaluated:
May 6, 2021
Accession:
VCV000224580.10
Variation ID:
224580
Description:
single nucleotide variant
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NM_000179.3(MSH6):c.1847C>G (p.Ser616Cys)

Allele ID
226304
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p16.3
Genomic location
2: 47799830 (GRCh38) GRCh38 UCSC
2: 48026969 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.48026969C>G
NM_000179.2:c.1847C>G NP_000170.1:p.Ser616Cys missense
LRG_219:g.21684C>G
... more HGVS
Protein change
S616C, S486C, S314C
Other names
-
Canonical SPDI
NC_000002.12:47799829:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA068191
dbSNP: rs772363120
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts May 6, 2021 RCV000410099.2
Uncertain significance 1 criteria provided, single submitter Nov 20, 2015 RCV000210205.3
Uncertain significance 1 criteria provided, single submitter Oct 30, 2020 RCV000524121.5
Uncertain significance 1 criteria provided, single submitter Jun 25, 2020 RCV001284178.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Apr 4, 2019 RCV000575424.3
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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
5678 5712

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Nov 20, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266203.1
Submitted: (Mar 03, 2016)
Evidence details
Uncertain significance
(Oct 03, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal cancer type 5
Allele origin: unknown
Counsyl
Accession: SCV000489415.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000283732.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces serine with cysteine at codon 616 of the MSH6 protein (p.Ser616Cys). The serine residue is weakly conserved and there is a … (more)
Uncertain significance
(Apr 04, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000908382.2
Submitted: (May 19, 2020)
Evidence details
Likely benign
(Oct 08, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000662410.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(Jun 25, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469819.1
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (1)
Uncertain significance
(May 06, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal cancer type 5
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV001737487.1
Submitted: (Jun 15, 2021)
Evidence details
Comment:
The MSH6 c.1847C>G (p.Ser616Cys) missense change has a maximum subpopulation frequency of 0.042% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-48026969-C-G?dataset=gnomad_r2_1). Six of seven in silico tools predict a … (more)

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
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Improving performance of multigene panels for genomic analysis of cancer predisposition. Shirts BH Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26845104

Text-mined citations for rs772363120...

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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 Oct 30, 2021