ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.3475dup (p.Tyr1159fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.3475dup (p.Tyr1159fs)
Variation ID: 1731773 Accession: VCV001731773.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47804944-47804945 (GRCh38) [ NCBI UCSC ] 2: 48032083-48032084 (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 Nov 29, 2022 May 1, 2024 Feb 15, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.3475dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Tyr1159fs frameshift NM_000179.2:c.3475dupT frameshift NM_001281492.2:c.3085dup NP_001268421.1:p.Tyr1029fs frameshift NM_001281493.2:c.2569dup NP_001268422.1:p.Tyr857fs frameshift NM_001281494.2:c.2569dup NP_001268423.1:p.Tyr857fs frameshift NM_001406795.1:c.3571dup NP_001393724.1:p.Tyr1191Leufs frameshift NM_001406796.1:c.3475dup NP_001393725.1:p.Tyr1159Leufs frameshift NM_001406797.1:c.3178dup NP_001393726.1:p.Tyr1060Leufs frameshift NM_001406798.1:c.3301dup NP_001393727.1:p.Tyr1101Leufs frameshift NM_001406799.1:c.2950dup NP_001393728.1:p.Tyr984Leufs frameshift NM_001406800.1:c.3475dup NP_001393729.1:p.Tyr1159Leufs frameshift NM_001406801.1:c.3178dup NP_001393730.1:p.Tyr1060Leufs frameshift NM_001406802.1:c.3571dup NP_001393731.1:p.Tyr1191Leufs frameshift NM_001406803.1:c.2611dup NP_001393732.1:p.Tyr871Leufs frameshift NM_001406804.1:c.3397dup NP_001393733.1:p.Tyr1133Leufs frameshift NM_001406805.1:c.3178dup NP_001393734.1:p.Tyr1060Leufs frameshift NM_001406806.1:c.2950dup NP_001393735.1:p.Tyr984Leufs frameshift NM_001406807.1:c.2950dup NP_001393736.1:p.Tyr984Leufs frameshift NM_001406808.1:c.3475dup NP_001393737.1:p.Tyr1159Leufs frameshift NM_001406809.1:c.3475dup NP_001393738.1:p.Tyr1159Leufs frameshift NM_001406811.1:c.2569dup NP_001393740.1:p.Tyr857Leufs frameshift NM_001406812.1:c.2569dup NP_001393741.1:p.Tyr857Leufs frameshift NM_001406813.1:c.3481dup NP_001393742.1:p.Tyr1161Leufs frameshift NM_001406814.1:c.2569dup NP_001393743.1:p.Tyr857Leufs frameshift NM_001406815.1:c.2569dup NP_001393744.1:p.Tyr857Leufs frameshift NM_001406816.1:c.2569dup NP_001393745.1:p.Tyr857Leufs frameshift NM_001406817.1:c.1909dup NP_001393746.1:p.Tyr637Leufs frameshift NM_001406818.1:c.3178dup NP_001393747.1:p.Tyr1060Leufs frameshift NM_001406819.1:c.3178dup NP_001393748.1:p.Tyr1060Leufs frameshift NM_001406820.1:c.3178dup NP_001393749.1:p.Tyr1060Leufs frameshift NM_001406821.1:c.3178dup NP_001393750.1:p.Tyr1060Leufs frameshift NM_001406822.1:c.3178dup NP_001393751.1:p.Tyr1060Leufs frameshift NM_001406823.1:c.2569dup NP_001393752.1:p.Tyr857Leufs frameshift NM_001406824.1:c.3178dup NP_001393753.1:p.Tyr1060Leufs frameshift NM_001406825.1:c.3178dup NP_001393754.1:p.Tyr1060Leufs frameshift NM_001406826.1:c.3307dup NP_001393755.1:p.Tyr1103Leufs frameshift NM_001406827.1:c.3178dup NP_001393756.1:p.Tyr1060Leufs frameshift NM_001406828.1:c.3178dup NP_001393757.1:p.Tyr1060Leufs frameshift NM_001406829.1:c.2569dup NP_001393758.1:p.Tyr857Leufs frameshift NM_001406830.1:c.3178dup NP_001393759.1:p.Tyr1060Leufs frameshift NM_001406831.1:c.256dup NP_001393760.1:p.Tyr86Leufs frameshift NM_001406832.1:c.322dup NP_001393761.1:p.Tyr108Leufs frameshift NM_001407362.1:c.1420dup NP_001394291.1:p.Tyr474Leufs frameshift NR_176256.1:n.2405dup NR_176257.1:n.3736dup NR_176258.1:n.3665dup NR_176259.1:n.3564dup NR_176260.1:n.1509dup NC_000002.12:g.47804946dup NC_000002.11:g.48032085dup NG_007111.1:g.26800dup NG_008397.1:g.105731dup LRG_219:g.26800dup LRG_219t1:c.3475dup LRG_219p1:p.Tyr1159Leufs - Protein change
- Y1029fs, Y1159fs, Y857fs
- Other names
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- Canonical SPDI
- NC_000002.12:47804944:TT:TTT
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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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- Links
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
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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
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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 (1) |
criteria provided, single submitter
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Feb 15, 2018 | RCV002457313.2 |
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
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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
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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
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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 15, 2018)
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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: SCV002613096.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.3475dupT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a duplication of T at nucleotide position 3475, causing a … (more)
The c.3475dupT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a duplication of T at nucleotide position 3475, causing a translational frameshift with a predicted alternate stop codon (p.Y1159Lfs*5). This alteration has been reported in the germline of a male diagnosed with MSI-high colorectal cancer at age 44; this tumor also demonstrated loss of MSH6 protein on immunohistochemistry (Siraj AK et al. Cancer, 2015 Jun;121:1762-71). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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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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Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer. | Siraj AK | Cancer | 2015 | PMID: 25712738 |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.