ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.4001G>A (p.Arg1334Gln)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.4001G>A (p.Arg1334Gln)
Variation ID: 89506 Accession: VCV000089506.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47806651 (GRCh38) [ NCBI UCSC ] 2: 48033790 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 24, 2015 Aug 11, 2024 Sep 5, 2013 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.4001G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Arg1334Gln missense NM_001281492.2:c.3611G>A NP_001268421.1:p.Arg1204Gln missense NM_001281493.2:c.3095G>A NP_001268422.1:p.Arg1032Gln missense NM_001281494.2:c.3095G>A NP_001268423.1:p.Arg1032Gln missense NC_000002.12:g.47806651G>A NC_000002.11:g.48033790G>A NG_007111.1:g.28505G>A NG_008397.1:g.104025C>T LRG_219:g.28505G>A LRG_219t1:c.4001G>A LRG_219p1:p.Arg1334Gln - Protein change
- R1334Q, R1204Q, R1032Q
- Other names
- p.R1334Q:CGG>CAG
- Canonical SPDI
- NC_000002.12:47806650:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9153 | 9466 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
reviewed by expert panel
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Sep 5, 2013 | RCV000074974.8 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000160701.15 | |
Uncertain significance (1) |
no assertion criteria provided
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- | RCV000202090.5 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 18, 2023 | RCV000491705.11 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 9, 2024 | RCV000576708.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 31, 2023 | RCV000542786.10 | |
Pathogenic (2) |
criteria provided, single submitter
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Aug 23, 2022 | RCV001355904.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 05, 2013)
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reviewed by expert panel
Method: research
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Lynch Syndrome
Affected status: unknown
Allele origin:
germline
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International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000108190.3
First in ClinVar: Dec 19, 2013 Last updated: Dec 24, 2022
Comment:
Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs
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Comment:
Multifactorial likelihood analysis posterior probability >0.99
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Pathogenic
(Aug 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Endometrial carcinoma
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004198133.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Apr 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002017592.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004835194.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This variant causes a G>A nucleotide substitution at the last nucleotide of exon 9 of the MSH6 gene. Splice site prediction tools suggest that this … (more)
This variant causes a G>A nucleotide substitution at the last nucleotide of exon 9 of the MSH6 gene. Splice site prediction tools suggest that this variant may impact RNA splicing. A RT-PCR analysis of RNA derived from two carriers has reported out-of-frame skipping of exon 9 (UMD database, http://139.124.156.133/4D_molecules/UMD230309.html). This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 12547705, 17453009, 18566915, 27601186; UMD database) and in individuals affected with endometrial cancer (PMID: 33467402) and colorectal cancer (PMID: 26681312). Multifactorial likelihood model using health history, in silico, and experimental data has suggested this variant has a high probability of being pathogenic (InSiGHT database, http://insight-database.org/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 2
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Pathogenic
(Mar 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000580100.6
First in ClinVar: Jun 25, 2017 Last updated: May 01, 2024 |
Comment:
The c.4001G>A pathogenic mutation (also known as p.R1334Q), located in coding exon 9 of the MSH6 gene, results from a G to A substitution at … (more)
The c.4001G>A pathogenic mutation (also known as p.R1334Q), located in coding exon 9 of the MSH6 gene, results from a G to A substitution at nucleotide position 4001. The amino acid change results in arginine to glutamine at codon 1334, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 9, which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This mutation has been reported in multiple Lynch syndrome patients as well as families and this variant segregated with disease in these families (Wijnen J et al. Nat Genet. 1999;23(2):142-144; Gille et al. Br J Cancer. 2002;87(8):892-897; Overbeek LI et al. Br J Cancer. 2007;96(10):1605-1612; Lagerstedt-Robinson K et al. Oncol. Rep. 2016 Nov;36(5):2823-2835). Functional studies have also demonstrated the pathogenicity of this variant (Houlleberghs H et al. PLoS Genet. 2017 May;13(5):e1006765). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jun 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000711435.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The p.Arg1334Gln variant in MSH6 has been reported in 4 individuals with MSH6-as sociated cancers and segregated with disease in 7 affected relatives from 2 … (more)
The p.Arg1334Gln variant in MSH6 has been reported in 4 individuals with MSH6-as sociated cancers and segregated with disease in 7 affected relatives from 2 fami lies (Hendriks 2004, Overbeek 2007, van Puijenbroek 2008, Klarskov 2011). It was absent from large population studies. This variant affects the last base of the exon, which is part of the 5? splice region and computational tools predict alt ered splicing, which is expected to lead to an altered or absent protein. Consis tent with this, tumors from patients harboring this variant showed absence of MS H6 protein (Hendriks 2004, Klarskov 2011). This variant was classified as Pathog enic on Sept 5, 2013 by the ClinGen-approved InSiGHT Expert Panel (ClinVar SCV00 0108190.2). In summary, this variant meets criteria to be classified as pathogen ic for Lynch syndrome. ACMG/AMP criteria applied: PP1_Str, PS4_Mod, PM2, PS3_Mod , PP3 (Richards 2015). (less)
Number of individuals with the variant: 4
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Likely pathogenic
(Mar 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677749.2
First in ClinVar: Jan 07, 2018 Last updated: Dec 24, 2022 |
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Pathogenic
(Feb 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000211330.16
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
Not observed in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant does … (more)
Not observed in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21081928, 23621914, 24362816, 18566915, 12547705, 15236168, 12373605, 20028993, 18415027, 27601186, 24705251, 26681312, 28502729, 24728189, 27768684, 17453009, 30283497, 29887214, 10508506, 8063241, 21836479, 31297337, 31447099, 32719484, 21120944, 17531815, 12019211, 34178123, 30787465) (less)
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Pathogenic
(Mar 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004018973.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. This variant is strongly associated with more severe personal … (more)
This variant is considered pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752]. (less)
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Pathogenic
(Jun 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004222027.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The MSH6 c.4001G>A (p.Arg1334Gln) variant has been reported in the published literature in affected individuals with colorectal cancer (PMIDs: 12373605 (2002), 15236168 (2004), 17453009 (2007), … (more)
The MSH6 c.4001G>A (p.Arg1334Gln) variant has been reported in the published literature in affected individuals with colorectal cancer (PMIDs: 12373605 (2002), 15236168 (2004), 17453009 (2007), 21836479 (2011), 26681312 (2015), 30264118 (2018), 31447099 (2019), and 34178123 (2021)), breast cancer (PMIDs: 26681312 (2015) and 33471991)), endometrial cancer (PMIDs: 10508506 (1999) and 15236168 (2004), 33467402 (2021)), lung cancer (PMID: 31297337 (2019)), as well as in individuals diagnosed with Lynch Syndrome (PMIDs: 18566915 (2009), 20028993 (2010), and 27601186 (2016)). It was also found in a tumor as a somatic variant (PMID: 29887214 (2018)). Functional studies have demonstrated that this variant is damaging to protein function (PMIDs: 185669115 (2009), 28531214 (2017), and 30264118 (2018)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Dec 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000624960.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1334 of the MSH6 protein (p.Arg1334Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1334 of the MSH6 protein (p.Arg1334Gln). RNA analysis indicates that this missense change induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Lynch syndrome (LS) and LS-associated cancers (PMID: 10508506, 15236168, 17453009, 21081928, 21836479, 26681312). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 89506). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 23621914). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 9 and introduces a new termination codon (Invitae). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000690430.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant causes a G>A nucleotide substitution at the last nucleotide of exon 9 of the MSH6 gene. Splice site prediction tools suggest that this … (more)
This variant causes a G>A nucleotide substitution at the last nucleotide of exon 9 of the MSH6 gene. Splice site prediction tools suggest that this variant may impact RNA splicing. A RT-PCR analysis of RNA derived from two carriers has reported out-of-frame skipping of exon 9 (UMD database, http://139.124.156.133/4D_molecules/UMD230309.html). This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 12547705, 17453009, 18566915, 27601186; UMD database) and in individuals affected with endometrial cancer (PMID: 33467402) and colorectal cancer (PMID: 26681312). Multifactorial likelihood model using health history, in silico, and experimental data has suggested this variant has a high probability of being pathogenic (InSiGHT database, http://insight-database.org/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jul 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005090507.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
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Pathogenic
(Aug 09, 2024)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Department of Human Genetics, Hannover Medical School
Accession: SCV005186167.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Clinical Features:
Endometrial carcinoma (present)
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Uncertain significance
(-)
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no assertion criteria provided
Method: research
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not specified
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257296.1
First in ClinVar: Nov 20, 2015 Last updated: Nov 20, 2015 |
Number of individuals with the variant: 1
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Endometrial carcinoma
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550922.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The MSH6 p.Arg1334Gln variant was identified in 5 of 3358 proband chromosomes (frequency: 0.001) from Dutch, Danish and Norwegian individuals or families with HNPCC (Wijnen_1999_10508506, … (more)
The MSH6 p.Arg1334Gln variant was identified in 5 of 3358 proband chromosomes (frequency: 0.001) from Dutch, Danish and Norwegian individuals or families with HNPCC (Wijnen_1999_10508506, Nilbert_2009_18566915, Gille_2002_12373605 , Hendriks_2004_15236168, Overbeek_2007_17453009). A bioinformatics tool, CoDP (Combination of the Different Properties), that integrates the prediction results of three methods, namely MAPP, PolyPhen-2 and SIFT and two other structural properties, found the variant had no impact on the MSH6 protein (Terui_2013_23621914). The variant was also identified in dbSNP (ID: rs267608122) “With Likely pathogenic,Pathogenic allele”, ClinVar (classified as pathogenic, reviewed by an expert panel(2013); submitters: pathogenic by InSIGHT and Ambry Genetics, likely pathogenic by GeneDx and uncertain significance by Mayo Clinic Genetic Testing Laboratories), Clinvitae (4x), Cosmic (1x in a glioma), UMD-LSDB (4x as causal), Mismatch Repair Genes Variant Database, and Insight Hereditary Tumors Database (9x). The variant was not identified in GeneInsight-COGR, MutDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Arg1334 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact of the variant Gln to the protein; this information is not very predictive of pathogenicity. The p.Arg1334Gln variant occurs in the last nucleotide of the exon. This position has been shown to be part of the splicing consensus sequence and variants involving this position sometimes affect splicing. In addition, 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932998.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953985.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Development and external validation of a novel nomogram for screening Chinese Lynch syndrome: based on a multicenter, population study. | Yang M | Therapeutic advances in medical oncology | 2021 | PMID: 34178123 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort. | Lawrence J | Current oncology (Toronto, Ont.) | 2021 | PMID: 33467402 |
Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
Identification of Germline Mismatch Repair Gene Mutations in Lung Cancer Patients With Paired Tumor-Normal Next Generation Sequencing: A Retrospective Study. | Sun S | Frontiers in oncology | 2019 | PMID: 31297337 |
Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing. | Mersch J | JAMA | 2018 | PMID: 30264118 |
Using Somatic Mutations from Tumors to Classify Variants in Mismatch Repair Genes. | Shirts BH | American journal of human genetics | 2018 | PMID: 29887214 |
Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity. | Houlleberghs H | PLoS genetics | 2017 | PMID: 28531214 |
Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population. | Lagerstedt-Robinson K | Oncology reports | 2016 | PMID: 27601186 |
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 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
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 |
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 |
Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function. | Klarskov L | The American journal of surgical pathology | 2011 | PMID: 21836479 |
Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats. | You JF | British journal of cancer | 2010 | PMID: 21081928 |
Risks of Lynch syndrome cancers for MSH6 mutation carriers. | Baglietto L | Journal of the National Cancer Institute | 2010 | PMID: 20028993 |
Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population. | Nilbert M | Familial cancer | 2009 | PMID: 18566915 |
Genome-wide copy neutral LOH is infrequent in familial and sporadic microsatellite unstable carcinomas. | van Puijenbroek M | Familial cancer | 2008 | PMID: 18415027 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer. | Overbeek LI | British journal of cancer | 2007 | PMID: 17453009 |
Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. | Hendriks YM | Gastroenterology | 2004 | PMID: 15236168 |
Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. | Hendriks Y | The American journal of pathology | 2003 | PMID: 12547705 |
Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach. | Gille JJ | British journal of cancer | 2002 | PMID: 12373605 |
Familial endometrial cancer in female carriers of MSH6 germline mutations. | Wijnen J | Nature genetics | 1999 | PMID: 10508506 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Endometrial cancer in four sisters: report of a kindred with presumed cancer family syndrome. | Menko FH | Gynecologic oncology | 1994 | PMID: 8063241 |
http://www.insight-database.org/classifications/index.html?gene=MSH6&variant=c.4001G%3EA | - | - | - | - |
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Text-mined citations for rs267608122 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.