The c.3472_3479delTGTTACGT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a deletion of 8 nucleotides at nucleotide positions 3472 to 3479, causing a translational frameshift with a predicted alternate stop codon (p.C1158Pfs*3). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.3472_3479del (p.Cys1158fs)
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.3472_3479del (p.Cys1158fs)
Variation ID: 2567471 Accession: VCV002567471.2
- Type and length
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Deletion, 8 bp
- Location
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Cytogenetic: 2p16.3 2: 47804941-47804948 (GRCh38) [ NCBI UCSC ] 2: 48032080-48032087 (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 Jul 8, 2023 May 1, 2024 May 12, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.3472_3479del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Cys1158fs frameshift NM_001281492.2:c.3082_3089del NP_001268421.1:p.Cys1028fs frameshift NM_001281493.2:c.2566_2573del NP_001268422.1:p.Cys856fs frameshift NM_001281494.2:c.2566_2573del NP_001268423.1:p.Cys856fs frameshift NM_001406795.1:c.3568_3575del NP_001393724.1:p.Cys1190fs frameshift NM_001406796.1:c.3472_3479del NP_001393725.1:p.Cys1158fs frameshift NM_001406797.1:c.3175_3182del NP_001393726.1:p.Cys1059fs frameshift NM_001406798.1:c.3298_3305del NP_001393727.1:p.Cys1100fs frameshift NM_001406799.1:c.2947_2954del NP_001393728.1:p.Cys983fs frameshift NM_001406800.1:c.3472_3479del NP_001393729.1:p.Cys1158fs frameshift NM_001406801.1:c.3175_3182del NP_001393730.1:p.Cys1059fs frameshift NM_001406802.1:c.3568_3575del NP_001393731.1:p.Cys1190fs frameshift NM_001406803.1:c.2608_2615del NP_001393732.1:p.Cys870fs frameshift NM_001406804.1:c.3394_3401del NP_001393733.1:p.Cys1132fs frameshift NM_001406805.1:c.3175_3182del NP_001393734.1:p.Cys1059fs frameshift NM_001406806.1:c.2947_2954del NP_001393735.1:p.Cys983fs frameshift NM_001406807.1:c.2947_2954del NP_001393736.1:p.Cys983fs frameshift NM_001406808.1:c.3472_3479del NP_001393737.1:p.Cys1158fs frameshift NM_001406809.1:c.3472_3479del NP_001393738.1:p.Cys1158fs frameshift NM_001406811.1:c.2566_2573del NP_001393740.1:p.Cys856fs frameshift NM_001406812.1:c.2566_2573del NP_001393741.1:p.Cys856fs frameshift NM_001406813.1:c.3478_3485del NP_001393742.1:p.Cys1160fs frameshift NM_001406814.1:c.2566_2573del NP_001393743.1:p.Cys856fs frameshift NM_001406815.1:c.2566_2573del NP_001393744.1:p.Cys856fs frameshift NM_001406816.1:c.2566_2573del NP_001393745.1:p.Cys856fs frameshift NM_001406817.1:c.1906_1913del NP_001393746.1:p.Cys636fs frameshift NM_001406818.1:c.3175_3182del NP_001393747.1:p.Cys1059fs frameshift NM_001406819.1:c.3175_3182del NP_001393748.1:p.Cys1059fs frameshift NM_001406820.1:c.3175_3182del NP_001393749.1:p.Cys1059fs frameshift NM_001406821.1:c.3175_3182del NP_001393750.1:p.Cys1059fs frameshift NM_001406822.1:c.3175_3182del NP_001393751.1:p.Cys1059fs frameshift NM_001406823.1:c.2566_2573del NP_001393752.1:p.Cys856fs frameshift NM_001406824.1:c.3175_3182del NP_001393753.1:p.Cys1059fs frameshift NM_001406825.1:c.3175_3182del NP_001393754.1:p.Cys1059fs frameshift NM_001406826.1:c.3304_3311del NP_001393755.1:p.Cys1102fs frameshift NM_001406827.1:c.3175_3182del NP_001393756.1:p.Cys1059fs frameshift NM_001406828.1:c.3175_3182del NP_001393757.1:p.Cys1059fs frameshift NM_001406829.1:c.2566_2573del NP_001393758.1:p.Cys856fs frameshift NM_001406830.1:c.3175_3182del NP_001393759.1:p.Cys1059fs frameshift NM_001406831.1:c.253_260del NP_001393760.1:p.Cys85fs frameshift NM_001406832.1:c.319_326del NP_001393761.1:p.Cys107fs frameshift NM_001407362.1:c.1417_1424del NP_001394291.1:p.Cys473fs frameshift NR_176256.1:n.2402_2409del non-coding transcript variant NR_176257.1:n.3733_3740del non-coding transcript variant NR_176258.1:n.3662_3669del non-coding transcript variant NR_176259.1:n.3561_3568del non-coding transcript variant NR_176260.1:n.1506_1513delTGTTACGT NC_000002.12:g.47804943_47804950del NC_000002.11:g.48032082_48032089del NG_007111.1:g.26797_26804del NG_008397.1:g.105728_105735del LRG_219:g.26797_26804del LRG_219t1:c.3472_3479del LRG_219p1:p.Cys1158Profs - Protein change
- C107fs, C1100fs, C856fs, C1102fs, C473fs, C636fs, C85fs, C1028fs, C1132fs, C1158fs, C1190fs, C983fs, C1059fs, C1160fs, C870fs
- Other names
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- Canonical SPDI
- NC_000002.12:47804940:GTTGTTACGT:GT
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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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May 12, 2023 | RCV003278518.2 |
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 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
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Ambry Genetics
Accession: SCV004007717.2
First in ClinVar: Jul 08, 2023 Last updated: May 01, 2024 |
Comment:
The c.3472_3479delTGTTACGT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a deletion of 8 nucleotides at nucleotide positions 3472 to … (more)
The c.3472_3479delTGTTACGT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a deletion of 8 nucleotides at nucleotide positions 3472 to 3479, causing a translational frameshift with a predicted alternate stop codon (p.C1158Pfs*3). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.3472_3479delTGTTACGT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a deletion of 8 nucleotides at nucleotide positions 3472 to 3479, causing a translational frameshift with a predicted alternate stop codon (p.C1158Pfs*3). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.