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NM_000179.3(MSH6):c.3753_3756dup (p.Val1253fs)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Mar 31, 2021)
Last evaluated:
May 28, 2019
Accession:
VCV000234794.6
Variation ID:
234794
Description:
4bp duplication
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NM_000179.3(MSH6):c.3753_3756dup (p.Val1253fs)

Allele ID
231582
Variant type
Duplication
Variant length
4 bp
Cytogenetic location
2p16.3
Genomic location
2: 47806309-47806310 (GRCh38) GRCh38 UCSC
2: 48033448-48033449 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000179.2:c.3753_3756dupATTA frameshift
NC_000002.11:g.48033449_48033452dup
NC_000002.12:g.47806310_47806313dup
... more HGVS
Protein change
V1253fs, V1123fs, V951fs
Other names
-
Canonical SPDI
NC_000002.12:47806309:ATTA:ATTAATTA
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA071953
dbSNP: rs876661222
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, multiple submitters, no conflicts May 28, 2019 RCV000576807.2
Pathogenic 1 criteria provided, single submitter Aug 23, 2016 RCV000216513.1
Likely pathogenic 1 criteria provided, single submitter Jul 2, 2018 RCV000502952.3
Pathogenic 1 criteria provided, single submitter Mar 13, 2019 RCV000566381.1
Pathogenic 1 criteria provided, single submitter May 17, 2018 RCV000690322.1
Pathogenic 1 no assertion criteria provided - RCV001353594.1
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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
Likely pathogenic
(Jan 16, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal cancer type 5
Allele origin: unknown
Counsyl
Accession: SCV000677835.1
Submitted: (Jun 22, 2017)
Evidence details
Pathogenic
(Aug 23, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000279830.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This duplication of four nucleotides in MSH6 is denoted c.3753_3756dupATTA at the cDNA level and p.Val1253IlefsX23 (V1253IfsX23) at the protein level. The normal sequence, with … (more)
Pathogenic
(Mar 13, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000662520.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.3753_3756dupATTA pathogenic mutation, located in coding exon 8 of the MSH6 gene, results from a duplication of ATTA at nucleotide position 3753, causing a … (more)
Pathogenic
(May 17, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
Invitae
Accession: SCV000818004.1
Submitted: (Aug 29, 2018)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change creates a premature translational stop signal (p.Val1253Ilefs*23) in the MSH6 gene. It is expected to result in an absent or disrupted protein … (more)
Likely pathogenic
(Jul 02, 2018)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome
Allele origin: unknown
Mendelics
Accession: SCV000837921.1
Submitted: (Aug 20, 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: SCV001135847.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Endometrial carcinoma
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592655.2
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The MSH6 p.Val1253IlefsX23 variant was not identified in the literature nor was it identified in dbSNP, (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant … (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

Text-mined citations for rs876661222...

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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