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NM_000179.3(MSH6):c.1634_1635del (p.Lys545fs)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Sep 25, 2021)
Last evaluated:
Aug 5, 2020
Accession:
VCV000140961.12
Variation ID:
140961
Description:
2bp deletion
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NM_000179.3(MSH6):c.1634_1635del (p.Lys545fs)

Allele ID
150675
Variant type
Deletion
Variant length
2 bp
Cytogenetic location
2p16.3
Genomic location
2: 47799614-47799615 (GRCh38) GRCh38 UCSC
2: 48026753-48026754 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000179.2:c.1634_1635delAA frameshift
LRG_219:g.21471_21472del
NC_000002.11:g.48026756_48026757del
... more HGVS
Protein change
K243fs, K545fs, K415fs
Other names
-
Canonical SPDI
NC_000002.12:47799613:AAAAA:AAA
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA008960
dbSNP: rs267608064
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jan 15, 2020 RCV000129244.6
Pathogenic 3 criteria provided, multiple submitters, no conflicts Jun 15, 2020 RCV000202281.5
Pathogenic 1 criteria provided, single submitter Aug 5, 2020 RCV000558194.6
Likely pathogenic 1 criteria provided, single submitter Jul 2, 2018 RCV000708867.1
Likely pathogenic 1 criteria provided, single submitter May 28, 2019 RCV000986717.1
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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
5678 5712

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jun 27, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184003.7
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (2)
Comment:
​The c.1634_1635delAA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of 2 nucleotides at positions 1634 and 1635 … (more)
Likely pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome
Allele origin: unknown
Mendelics
Accession: SCV000837882.1
Submitted: (Aug 20, 2018)
Evidence details
Pathogenic
(Feb 26, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601511.2
Submitted: (Aug 31, 2018)
Evidence details
Likely pathogenic
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal cancer type 5
Allele origin: unknown
Mendelics
Accession: SCV001135809.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(Jan 15, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000905450.2
Submitted: (May 19, 2020)
Comment:
This variant deletes 2 nucleotides in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
Evidence details
Pathogenic
(Aug 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000624671.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change creates a premature translational stop signal (p.Lys545Argfs*17) in the MSH6 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Jun 15, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565783.4
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
not provided
Allele origin: unknown
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257215.1
Submitted: (Nov 19, 2015)
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
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
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
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
Compound heterozygosity for MSH6 mutations in a pediatric lymphoma patient. Peters A Journal of pediatric hematology/oncology 2009 PMID: 19194194
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

Text-mined citations for rs267608064...

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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 24, 2021