The c.2342dupC variant, located in coding exon 4 of the MSH6 gene, results from a duplication of C at nucleotide position 2342, causing a translational frameshift with a predicted alternate stop codon (p.L782Tfs*3). 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.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2342dup (p.Leu782fs)
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)
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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.2342dup (p.Leu782fs)
Variation ID: 1789889 Accession: VCV001789889.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47800321-47800322 (GRCh38) [ NCBI UCSC ] 2: 48027460-48027461 (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 May 16, 2019 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.2342dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Leu782fs frameshift NM_000179.2:c.2342dupC frameshift NM_001281492.2:c.1952dup NP_001268421.1:p.Leu652fs frameshift NM_001281493.2:c.1436dup NP_001268422.1:p.Leu480fs frameshift NM_001281494.2:c.1436dup NP_001268423.1:p.Leu480fs frameshift NM_001406795.1:c.2438dup NP_001393724.1:p.Leu814Thrfs frameshift NM_001406796.1:c.2342dup NP_001393725.1:p.Leu782Thrfs frameshift NM_001406797.1:c.2045dup NP_001393726.1:p.Leu683Thrfs frameshift NM_001406798.1:c.2342dup NP_001393727.1:p.Leu782Thrfs frameshift NM_001406799.1:c.1817dup NP_001393728.1:p.Leu607Thrfs frameshift NM_001406800.1:c.2342dup NP_001393729.1:p.Leu782Thrfs frameshift NM_001406801.1:c.2045dup NP_001393730.1:p.Leu683Thrfs frameshift NM_001406802.1:c.2438dup NP_001393731.1:p.Leu814Thrfs frameshift NM_001406804.1:c.2264dup NP_001393733.1:p.Leu756Thrfs frameshift NM_001406805.1:c.2045dup NP_001393734.1:p.Leu683Thrfs frameshift NM_001406806.1:c.1817dup NP_001393735.1:p.Leu607Thrfs frameshift NM_001406807.1:c.1817dup NP_001393736.1:p.Leu607Thrfs frameshift NM_001406808.1:c.2342dup NP_001393737.1:p.Leu782Thrfs frameshift NM_001406809.1:c.2342dup NP_001393738.1:p.Leu782Thrfs frameshift NM_001406811.1:c.1436dup NP_001393740.1:p.Leu480Thrfs frameshift NM_001406812.1:c.1436dup NP_001393741.1:p.Leu480Thrfs frameshift NM_001406813.1:c.2348dup NP_001393742.1:p.Leu784Thrfs frameshift NM_001406814.1:c.1436dup NP_001393743.1:p.Leu480Thrfs frameshift NM_001406815.1:c.1436dup NP_001393744.1:p.Leu480Thrfs frameshift NM_001406816.1:c.1436dup NP_001393745.1:p.Leu480Thrfs frameshift NM_001406818.1:c.2045dup NP_001393747.1:p.Leu683Thrfs frameshift NM_001406819.1:c.2045dup NP_001393748.1:p.Leu683Thrfs frameshift NM_001406820.1:c.2045dup NP_001393749.1:p.Leu683Thrfs frameshift NM_001406821.1:c.2045dup NP_001393750.1:p.Leu683Thrfs frameshift NM_001406822.1:c.2045dup NP_001393751.1:p.Leu683Thrfs frameshift NM_001406823.1:c.1436dup NP_001393752.1:p.Leu480Thrfs frameshift NM_001406824.1:c.2045dup NP_001393753.1:p.Leu683Thrfs frameshift NM_001406825.1:c.2045dup NP_001393754.1:p.Leu683Thrfs frameshift NM_001406826.1:c.2174dup NP_001393755.1:p.Leu726Thrfs frameshift NM_001406827.1:c.2045dup NP_001393756.1:p.Leu683Thrfs frameshift NM_001406828.1:c.2045dup NP_001393757.1:p.Leu683Thrfs frameshift NM_001406829.1:c.1436dup NP_001393758.1:p.Leu480Thrfs frameshift NM_001406830.1:c.2045dup NP_001393759.1:p.Leu683Thrfs frameshift NR_176256.1:n.1204dup NR_176257.1:n.2431dup NR_176258.1:n.2431dup NR_176259.1:n.2431dup NR_176261.1:n.2431dup NC_000002.12:g.47800325dup NC_000002.11:g.48027464dup NG_007111.1:g.22179dup LRG_219:g.22179dup LRG_219t1:c.2342dup LRG_219p1:p.Leu782Thrfs - Protein change
- L480fs, L652fs, L782fs
- Other names
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- Canonical SPDI
- NC_000002.12:47800321:CCCC:CCCCC
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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 |
9159 | 9475 | |
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 (1) |
criteria provided, single submitter
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May 16, 2019 | RCV002428523.2 |
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
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
(May 16, 2019)
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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: SCV002731865.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2342dupC variant, located in coding exon 4 of the MSH6 gene, results from a duplication of C at nucleotide position 2342, causing a translational … (more)
The c.2342dupC variant, located in coding exon 4 of the MSH6 gene, results from a duplication of C at nucleotide position 2342, causing a translational frameshift with a predicted alternate stop codon (p.L782Tfs*3). 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)
|
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:
The c.2342dupC variant, located in coding exon 4 of the MSH6 gene, results from a duplication of C at nucleotide position 2342, causing a translational frameshift with a predicted alternate stop codon (p.L782Tfs*3). 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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
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.