This sequence change creates a premature translational stop signal (p.Met1153Ilefs*32) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency).
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.3458_3459insTA (p.Met1153fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.3458_3459insTA (p.Met1153fs)
Variation ID: 2099704 Accession: VCV002099704.2
- Type and length
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Insertion, 2 bp
- Location
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Cytogenetic: 2p16.3 2: 47804929-47804930 (GRCh38) [ NCBI UCSC ] 2: 48032068-48032069 (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 Feb 8, 2023 Feb 20, 2024 Feb 19, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.3458_3459insTA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Met1153fs frameshift NM_001281492.2:c.3068_3069insTA NP_001268421.1:p.Met1023fs frameshift NM_001281493.2:c.2552_2553insTA NP_001268422.1:p.Met851fs frameshift NM_001281494.2:c.2552_2553insTA NP_001268423.1:p.Met851fs frameshift NM_001406795.1:c.3554_3555insTA NP_001393724.1:p.Met1185Ilefs frameshift NM_001406796.1:c.3458_3459insTA NP_001393725.1:p.Met1153Ilefs frameshift NM_001406797.1:c.3161_3162insTA NP_001393726.1:p.Met1054Ilefs frameshift NM_001406798.1:c.3284_3285insTA NP_001393727.1:p.Met1095Ilefs frameshift NM_001406799.1:c.2933_2934insTA NP_001393728.1:p.Met978Ilefs frameshift NM_001406800.1:c.3458_3459insTA NP_001393729.1:p.Met1153Ilefs frameshift NM_001406801.1:c.3161_3162insTA NP_001393730.1:p.Met1054Ilefs frameshift NM_001406802.1:c.3554_3555insTA NP_001393731.1:p.Met1185Ilefs frameshift NM_001406803.1:c.2594_2595insTA NP_001393732.1:p.Met865Ilefs frameshift NM_001406804.1:c.3380_3381insTA NP_001393733.1:p.Met1127Ilefs frameshift NM_001406805.1:c.3161_3162insTA NP_001393734.1:p.Met1054Ilefs frameshift NM_001406806.1:c.2933_2934insTA NP_001393735.1:p.Met978Ilefs frameshift NM_001406807.1:c.2933_2934insTA NP_001393736.1:p.Met978Ilefs frameshift NM_001406808.1:c.3458_3459insTA NP_001393737.1:p.Met1153Ilefs frameshift NM_001406809.1:c.3458_3459insTA NP_001393738.1:p.Met1153Ilefs frameshift NM_001406811.1:c.2552_2553insTA NP_001393740.1:p.Met851Ilefs frameshift NM_001406812.1:c.2552_2553insTA NP_001393741.1:p.Met851Ilefs frameshift NM_001406813.1:c.3464_3465insTA NP_001393742.1:p.Met1155Ilefs frameshift NM_001406814.1:c.2552_2553insTA NP_001393743.1:p.Met851Ilefs frameshift NM_001406815.1:c.2552_2553insTA NP_001393744.1:p.Met851Ilefs frameshift NM_001406816.1:c.2552_2553insTA NP_001393745.1:p.Met851Ilefs frameshift NM_001406817.1:c.1892_1893insTA NP_001393746.1:p.Met631Ilefs frameshift NM_001406818.1:c.3161_3162insTA NP_001393747.1:p.Met1054Ilefs frameshift NM_001406819.1:c.3161_3162insTA NP_001393748.1:p.Met1054Ilefs frameshift NM_001406820.1:c.3161_3162insTA NP_001393749.1:p.Met1054Ilefs frameshift NM_001406821.1:c.3161_3162insTA NP_001393750.1:p.Met1054Ilefs frameshift NM_001406822.1:c.3161_3162insTA NP_001393751.1:p.Met1054Ilefs frameshift NM_001406823.1:c.2552_2553insTA NP_001393752.1:p.Met851Ilefs frameshift NM_001406824.1:c.3161_3162insTA NP_001393753.1:p.Met1054Ilefs frameshift NM_001406825.1:c.3161_3162insTA NP_001393754.1:p.Met1054Ilefs frameshift NM_001406826.1:c.3290_3291insTA NP_001393755.1:p.Met1097Ilefs frameshift NM_001406827.1:c.3161_3162insTA NP_001393756.1:p.Met1054Ilefs frameshift NM_001406828.1:c.3161_3162insTA NP_001393757.1:p.Met1054Ilefs frameshift NM_001406829.1:c.2552_2553insTA NP_001393758.1:p.Met851Ilefs frameshift NM_001406830.1:c.3161_3162insTA NP_001393759.1:p.Met1054Ilefs frameshift NM_001406831.1:c.239_240insTA NP_001393760.1:p.Met80Ilefs frameshift NM_001406832.1:c.305_306insTA NP_001393761.1:p.Met102Ilefs frameshift NM_001407362.1:c.1403_1404insTA NP_001394291.1:p.Met468Ilefs frameshift NR_176256.1:n.2388_2389insTA NR_176257.1:n.3719_3720insTA NR_176258.1:n.3648_3649insTA NR_176259.1:n.3547_3548insTA NR_176260.1:n.1492_1493insTA NC_000002.12:g.47804929_47804930insTA NC_000002.11:g.48032068_48032069insTA NG_007111.1:g.26783_26784insTA NG_008397.1:g.105746_105747insTA LRG_219:g.26783_26784insTA LRG_219t1:c.3458_3459insTA LRG_219p1:p.Met1153Ilefs - Protein change
- M1023fs, M1153fs, M851fs
- Other names
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- Canonical SPDI
- NC_000002.12:47804929::TA
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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
Help
The frequency of the allele represented by this VCV record.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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 |
9161 | 9479 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Feb 19, 2022 | RCV003021842.3 |
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
(Feb 19, 2022)
|
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: SCV003321142.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Met1153Ilefs*32) in the MSH6 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Met1153Ilefs*32) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). (less)
|
Comment:
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. |
Comment:
This sequence change creates a premature translational stop signal (p.Met1153Ilefs*32) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| 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 this variant ...
HelpRecord last updated Sep 29, 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.