ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2314C>T (p.Arg772Trp)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.2314C>T (p.Arg772Trp)
Variation ID: 89267 Accession: VCV000089267.61
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47800297 (GRCh38) [ NCBI UCSC ] 2: 48027436 (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 May 12, 2024 Oct 18, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.2314C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Arg772Trp missense NM_001281492.2:c.1924C>T NP_001268421.1:p.Arg642Trp missense NM_001281493.2:c.1408C>T NP_001268422.1:p.Arg470Trp missense NM_001281494.2:c.1408C>T NP_001268423.1:p.Arg470Trp missense NC_000002.12:g.47800297C>T NC_000002.11:g.48027436C>T NG_007111.1:g.22151C>T LRG_219:g.22151C>T LRG_219t1:c.2314C>T LRG_219p1:p.Arg772Trp P52701:p.Arg772Trp - Protein change
- R772W, R470W, R642W
- Other names
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- Canonical SPDI
- NC_000002.12:47800296:C:T
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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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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 |
9037 | 9343 |
Conditions - Germline
Condition
Help
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
Help
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
Help
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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Oct 18, 2018 | RCV000074732.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 12, 2023 | RCV000162422.14 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Sep 1, 2023 | RCV000218399.30 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 18, 2024 | RCV000524139.12 | |
Likely pathogenic (1) |
no assertion criteria provided
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- | RCV001353694.2 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 2, 2023 | RCV002467437.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 16, 2022 | RCV003466943.1 |
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
(Oct 18, 2018)
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reviewed by expert panel
Method: curation
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Lynch syndrome
Affected status: yes
Allele origin:
germline
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International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107941.3
First in ClinVar: Dec 19, 2013 Last updated: Jun 03, 2019 |
Comment:
Multifactorial likelihood analysis posterior probability >0.99
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Pathogenic
(Feb 15, 2019)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695806.3
First in ClinVar: Feb 19, 2018 Last updated: Jun 03, 2019 |
Comment:
Variant summary: MSH6 c.2314C>T (p.Arg772Trp) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, core domain of the encoded … (more)
Variant summary: MSH6 c.2314C>T (p.Arg772Trp) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, core domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function (ACMG PP3). The variant allele was found at a frequency of 8.1e-06 in 246050 control chromosomes (gnomAD and publication, ACMG PM2). c.2314C>T has been reported in the literature in individuals affected with Lynch Syndrome, colon cancer, endometrial cancer and breast cancer (Plaschke 2004, Buchanan 2014, Sunga 2017, Lu_2018). The reported patients ranged from those fulfilling the Amsterdam-II criteria (Jasperson 2008), revised Bethesda guidelines (Buchanan 2014) as well as not fulfilling the Bethesda guidelines (Plaschke 2004). In addition, in one comprehensively genotyped patient affected by colon and urinary bladder cancer who had reduced expression of the MSH6 protein within the tumor (and normal expression of MLH1 and MSH2) the variant was also found in her affected mother (Jasperson 2008). Loss of MSH6 expression in tumors was also noted in other studies for individuals carrying the variant (Plaschke 2004, Buchanan 2014). Furthermore, this variant has been reported in homozygous state associated with the phenotype for constitutional mismatch repair deficiency (CMMR-D) syndrome; immunohistochemical analysis of skin biopsies revealed MSH6 protein deficiency (Elhasid 2015, Levi 2015). The variant was also found in one female endometrial cancer patient (47 y.o.) as a somatic variant, who carried a frameshift 19bps insertion in MSH6 as a germ-line variant (Goodfellow 2003). Lastly, somatic point mutations affecting a different nucleotide but the same amino acid residue (c.2315G>A [p.R772Q]), have been identified in a colon and a gastric cancer, both with the MSI-H phenotype (Ohmiya et al., 2001). This points to p.Arg772Trp fulfilling the LOH (Loss of Heterozygosity) criteria for tumor suppressor genes and highlighting functional importance of this residue within the MSH6 protein. These data indicate that the variant is likely to be associated with disease (ACMG PS4). A co-occurrence with another pathogenic variant has been reported in our internal database (CHEK2 c.1434delA, p.Glu479fsX3). Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely pathogenic. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) has recently classified this variant as a class-5 pathogenic variant using the same evidence outlined above. Based on the evidence outlined above, the variant meets sufficient clinical criteria to be classified as pathogenic. (less)
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Pathogenic
(Nov 03, 2020)
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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: SCV000279102.9
First in ClinVar: May 29, 2016 Last updated: Feb 19, 2018 |
Comment:
Published functional studies demonstrate a damaging effect: deficient mismatch repair activity (Thompson 2020); Not observed at a significant frequency in large population cohorts (Lek 2016); … (more)
Published functional studies demonstrate a damaging effect: deficient mismatch repair activity (Thompson 2020); Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24323032, 29345684, 30212499, 30322717, 12732731, 18176851, 14974087, 26333163, 26274037, 25307252, 28449805, 28514183, 30128536, 27498913, 23621914, 30166433, 32849802, 32338768) (less)
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Pathogenic
(Dec 09, 2022)
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criteria provided, single submitter
Method: research
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Lynch syndrome 5
Affected status: no
Allele origin:
germline
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762823.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PS4_STR, PS3, PM2_SUP, PM5, PP1
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Pathogenic
(Aug 16, 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: SCV004185585.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered pathogenic. Functional studies indicate this variant impacts protein function [PMID: 31965077]. This variant is expected to disrupt protein structure [Myriad internal … (more)
This variant is considered pathogenic. Functional studies indicate this variant impacts protein function [PMID: 31965077]. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 18176851, 30166433, 25307252]. (less)
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Pathogenic
(Aug 16, 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: SCV004198135.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Oct 08, 2021)
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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: SCV001470348.2
First in ClinVar: Jan 26, 2021 Last updated: Jan 06, 2024 |
Comment:
The frequency of this variant in the general population, 0.000008 (2/251130 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been … (more)
The frequency of this variant in the general population, 0.000008 (2/251130 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with colorectal, breast, ovarian, endometrial, and prostate cancer (PMIDs: 32338768 (2020), 30128536 (2018), 30322717 (2018), 28449805 (2017), 24323032 (2014), 14974087 (2004)). It has also been reported in the homozygous state in three children with CMMRD (PMIDs: 26274037 (2015), 25307252 (2015)). Additionally, a functional study indicated this variant has significantly reduced DNA mismatch repair activity in vitro, and the variant was characterized as being pathogenic based on multifactorial analysis (PMID: 32849802 (2020)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jun 14, 2023)
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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: SCV002023525.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 23, 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: SCV000908396.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with tryptophan at codon 772 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with tryptophan at codon 772 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study has shown that this variant causes a significant loss of mismatch repair activity compared to wild type protein in a cell-free in vitro assay (PMID: 32849802). This variant has also been shown to have an incomplete impact on mRNA splicing, expressing both truncated and reference transcripts (PMID: 32849802). This variant has been reported in individuals affected with colorectal, endometrial, and bladder cancer (PMID: 14974087, 18176851, 24323032, 36293153), breast cancer (PMID: 30128536), and reported three times among a suspected Lynch syndrome cohort (PMID: 28514183). This variant has also been reported in homozygous carriers from families affected with constitutive mismatch repair deficiency syndrome (PMID: 25307252, 26274037, 30166433). This variant has been identified in 2/251130 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 18, 2024)
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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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Invitae
Accession: SCV000551232.11
First in ClinVar: Mar 24, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 772 of the MSH6 protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 772 of the MSH6 protein (p.Arg772Trp). This variant is present in population databases (rs63750138, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of Lynch syndrome and constitutional mismatch repair deficiency (PMID: 14974087, 18176851, 24323032, 25307252, 28449805, 28514183; Invitae). ClinVar contains an entry for this variant (Variation ID: 89267). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MSH6 protein function with a positive predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely Pathogenic
(Sep 13, 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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848534.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Arg772Trp variant in MSH6 has not been previously reported in 6 individuals with Lynch syndrome (LS) or LS-associated cancers and segregated with disease in … (more)
The p.Arg772Trp variant in MSH6 has not been previously reported in 6 individuals with Lynch syndrome (LS) or LS-associated cancers and segregated with disease in 1 affected relative from 1 family (Plaschke 2004 PMID: 14974087, Jasperson 2008 PMID: 18176851, Buchanan 2014 PMID: 24323032, Sunga 2017 PMID: 28449805, Carter 2018 PMID: 30322717, Nguyen-Dumont 2020 PMID: 32338768). Immunohistochemistry performed on tumors sampled from 4 individuals showed either reduction or loss of MSH6 expression (Plaschke 2004 PMID: 14974087, Jasperson 2008 PMID: 18176851, Buchanan 2014 PMID: 24323032). Additionally, this variant has been reported in 3 other individuals with a personal and/or family history of cancer who had been referred for germline cancer genetic testing (Espenschied 2017 PMID: 28514183). Furthermore, this variant has been reported as in the homozygous state in an individual with constitutional mismatch repair deficiency (CMMRD) and their sibling who had clinical features of the disease. Immunohistochemistry performed on skin biopsies from these children were found to be deficient in MSH6 expression (Elhasid 2015 PMID: 26274037). This variant has also been identified in 0.001% (1/68020) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, gnomAD v3.1.2). In vitro functional studies provide some evidence that this variant impairs mismatch repair activity (Thompson 2020 PMID: 32849802) and computational prediction tools and conservation analyses are consistent with pathogenicity. Moreover, this variant was classified as pathogenic on Oct 18, 2018 by the ClinGen-approved International Society for Gastrointestinal Hereditary Tumours (InSiGHT) expert panel (Variation ID 89267). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PS4_Moderate, PS3_Moderate, PM2_Supporting, PP3. (less)
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Pathogenic
(Nov 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: yes
Allele origin:
paternal
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV005016486.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
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Pathogenic
(Apr 12, 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
|
Ambry Genetics
Accession: SCV000212763.9
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.R772W variant (also known as c.2314C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide … (more)
The p.R772W variant (also known as c.2314C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 2314. The arginine at codon 772 is replaced by tryptophan, an amino acid with dissimilar properties. Residue 772 is located in a highly conserved loop of the Lever Domain in the MSH6 protein and is likely to be involved in signal transduction between ATPase and DNA binding domains (Warren JJ et al. Mol. Cell. 2007 May;26(4):579-92). This alteration was identified in a patient diagnosed with colon cancer at age 75 who had no family history of HNPCC-related cancers. Tumor studies showed MSI-High and absent MSH6 on IHC (Plaschke J et al. Hum Mutat. 2004 Mar;23(3):285). In another study, this alteration segregated with disease in a proband and her mother. The proband was diagnosed with colon cancer at age 45 and bladder cancer at age 47 that was MSI-Low with reduced expression of MSH6 on IHC. The proband's mother was diagnosed with endometrial cancer at age 38 and colon cancer at age 59 that showed reduced expression of MSH2 and MSH6 on IHC (Jasperson KW et al. Fam Cancer. 2008;7(4):281-5). In another study, this alteration was identified in an individual diagnosed with endometrial cancer at age 58 that showed loss of MSH6 on IHC (Buchanan DD et al. J Clin Oncol. 2014 Jan 10;32(2):90-100). The p.R772W alteration has also been reported as homozygous in multiple individuals with known familial consanguinity and clinical histories consistent with CMMR-D (Levi Z et al. Clin Genet. 2015 Nov;88(5):474-8; Elhasid R et al. J. Pediatr. Hematol. Oncol. 2015 Nov;37(8):e490-3). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Sep 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001250448.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
MSH6: PS4, PM1, PM2, PP3, PS3:Supporting
Number of individuals with the variant: 4
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691930.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
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: SCV000592604.2 First in ClinVar: Mar 24, 2015 Last updated: Apr 13, 2021 |
Comment:
The p.Arg772Trp variant was identified in the literature in 2 of 54 proband chromosomes (frequency 0.037) from individuals with colon cancer and was not identified … (more)
The p.Arg772Trp variant was identified in the literature in 2 of 54 proband chromosomes (frequency 0.037) from individuals with colon cancer and was not identified in 190 chromosomes from healthy control individuals (Jasperson 2008, Plaschke 2004). This variant was also reported in dbSNP (rs63750138) “with untested allele”, in the HGMD, “InSiGHT Colon Cancer Database”, the “MMR Genes Variant Database” and in the Exome Variant Server ESP Project with a frequency of 0.0007 in African American alleles, suggesting that this variant may be present at low frequency in certain populations of origin. Plaschke (2004) describes a patient with the variant who had loss of MSH6 protein expression in a late onset tumour of the colon, and suggests that that the late onset of disease in this patient may be interpreted as reduced penetrance of the variant. In another study, the p.Arg772Trp variant was identified as a somatic mutation in an individual with early onset endometrial cancer who also had a germline MSH6 mutation (Goodfellow 2003), and Jasperson (2008) suggests that the somatic variant in this patient’s tumour may have inactivated the wild-type allele, leading to the early onset of this cancer. A different variant at this amino acid position, p.Arg772Gln, was identified by Ohmiya (2001) in two cases as a somatic variant in one colon and one stomach tumor, increasing the likelihood that this position is important to MSH6 protein function. The p.Arg772 residue is conserved across mammals and lower organisms and computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) suggest that the p.Arg772Trp variant may impact the protein. In addition, this residue is noted to be situated within the DNA binding domain (Goodfellow 2003) and one in-silico study suggests that this variant likely has an affect on MSH6 function (Terui 2013). However, this information is not predictive enough to assume pathogenicity. This individual is reported as homozygous for this variant and had a skin biopsy that was reported as MSH6 deficient and also had weak MSH2 deficiency by immunohistochemistry and also had other features of biallelic mismatch repair (MMR) syndrome (café au-lait spots) increasing the likelihood this variant is pathogenic. Notably, this variant also segregated in homozygous form in an affected family member who also had features of biallelic MMR deficiency and an associated cancer (AML). In summary, based on the above information the clinical significance of this variant cannot be determined at this time although we would lean towards a more pathogenic role for this variant. Therefore this variant is classified as predicted pathogenic. (less)
Number of individuals with the variant: 2
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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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Lynch Syndrome Identification in Saudi Cohort of Endometrial Cancer Patients Screened by Universal Approach. | Bu R | International journal of molecular sciences | 2022 | PMID: 36293153 |
Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation. | Thompson BA | Frontiers in genetics | 2020 | PMID: 32849802 |
Rare germline genetic variants and risk of aggressive prostate cancer. | Nguyen-Dumont T | International journal of cancer | 2020 | PMID: 32338768 |
Two integrated and highly predictive functional analysis-based procedures for the classification of MSH6 variants in Lynch syndrome. | Drost M | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31965077 |
Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing. | Lu HM | JAMA oncology | 2019 | PMID: 30128536 |
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
Multiple Brain Developmental Venous Anomalies as a Marker for Constitutional Mismatch Repair Deficiency Syndrome. | Shiran SI | AJNR. American journal of neuroradiology | 2018 | PMID: 30166433 |
Multigene Panel Testing Provides a New Perspective on Lynch Syndrome. | Espenschied CR | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2017 | PMID: 28514183 |
Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome. | Sunga AY | Cancer genetics | 2017 | PMID: 28449805 |
Monogenic and polygenic determinants of sarcoma risk: an international genetic study. | Ballinger ML | The Lancet. Oncology | 2016 | PMID: 27498913 |
Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2. | Niroula A | Human mutation | 2015 | PMID: 26333163 |
Management of Acute Myeloblastic Leukemia in a Child With Biallelic Mismatch Repair Deficiency. | Elhasid R | Journal of pediatric hematology/oncology | 2015 | PMID: 26274037 |
The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer. | Levi Z | Clinical genetics | 2015 | PMID: 25307252 |
Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing. | Buchanan DD | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2014 | PMID: 24323032 |
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 |
Working through a diagnostic challenge: colonic polyposis, Amsterdam criteria, and a mismatch repair mutation. | Jasperson KW | Familial cancer | 2008 | PMID: 18176851 |
Eight novel MSH6 germline mutations in patients with familial and nonfamilial colorectal cancer selected by loss of protein expression in tumor tissue. | Plaschke J | Human mutation | 2004 | PMID: 14974087 |
Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. | Goodfellow PJ | Proceedings of the National Academy of Sciences of the United States of America | 2003 | PMID: 12732731 |
http://www.insight-database.org/classifications/?gene=MSH6&variant=c.2314C%3ET | - | - | - | - |
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Text-mined citations for rs63750138 ...
HelpRecord last updated May 12, 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.