The c.3572_3573dupTT pathogenic mutation, located in coding exon 7 of the MSH6 gene, results from a duplication of TT at nucleotide position 3572, causing a translational frameshift with a predicted alternate stop codon (p.V1192Lfs*4). 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.3572_3573dup (p.Val1192fs)
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.3572_3573dup (p.Val1192fs)
Variation ID: 3230559 Accession: VCV003230559.1
- Type and length
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Duplication, 2 bp
- Location
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Cytogenetic: 2p16.3 2: 48032767-48032768 (GRCh37) [ NCBI UCSC ] 2: 47805628-47805629 (GRCh38) [ 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 May 1, 2024 May 1, 2024 Feb 22, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.3572_3573dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Val1192fs frameshift NM_000179.2:c.3572_3573dupTT frameshift NM_001281492.2:c.3182_3183dup NP_001268421.1:p.Val1062fs frameshift NM_001281493.2:c.2666_2667dup NP_001268422.1:p.Val890fs frameshift NM_001281494.2:c.2666_2667dup NP_001268423.1:p.Val890fs frameshift NM_001406795.1:c.3668_3669dup NP_001393724.1:p.Val1224fs frameshift NM_001406796.1:c.3572_3573dup NP_001393725.1:p.Val1192fs frameshift NM_001406797.1:c.3275_3276dup NP_001393726.1:p.Val1093fs frameshift NM_001406798.1:c.3398_3399dup NP_001393727.1:p.Val1134fs frameshift NM_001406799.1:c.3047_3048dup NP_001393728.1:p.Val1017fs frameshift NM_001406800.1:c.3572_3573dup NP_001393729.1:p.Val1192fs frameshift NM_001406801.1:c.3275_3276dup NP_001393730.1:p.Val1093fs frameshift NM_001406802.1:c.3668_3669dup NP_001393731.1:p.Val1224fs frameshift NM_001406803.1:c.2708_2709dup NP_001393732.1:p.Val904fs frameshift NM_001406804.1:c.3494_3495dup NP_001393733.1:p.Val1166fs frameshift NM_001406805.1:c.3275_3276dup NP_001393734.1:p.Val1093fs frameshift NM_001406806.1:c.3047_3048dup NP_001393735.1:p.Val1017fs frameshift NM_001406807.1:c.3047_3048dup NP_001393736.1:p.Val1017fs frameshift NM_001406808.1:c.3572_3573dup NP_001393737.1:p.Val1192fs frameshift NM_001406809.1:c.3572_3573dup NP_001393738.1:p.Val1192fs frameshift NM_001406811.1:c.2666_2667dup NP_001393740.1:p.Val890fs frameshift NM_001406812.1:c.2666_2667dup NP_001393741.1:p.Val890fs frameshift NM_001406813.1:c.3578_3579dup NP_001393742.1:p.Val1194fs frameshift NM_001406814.1:c.2666_2667dup NP_001393743.1:p.Val890fs frameshift NM_001406815.1:c.2666_2667dup NP_001393744.1:p.Val890fs frameshift NM_001406816.1:c.2666_2667dup NP_001393745.1:p.Val890fs frameshift NM_001406817.1:c.2006_2007dup NP_001393746.1:p.Val670fs frameshift NM_001406818.1:c.3275_3276dup NP_001393747.1:p.Val1093fs frameshift NM_001406819.1:c.3275_3276dup NP_001393748.1:p.Val1093fs frameshift NM_001406820.1:c.3275_3276dup NP_001393749.1:p.Val1093fs frameshift NM_001406821.1:c.3275_3276dup NP_001393750.1:p.Val1093fs frameshift NM_001406822.1:c.3275_3276dup NP_001393751.1:p.Val1093fs frameshift NM_001406823.1:c.2666_2667dup NP_001393752.1:p.Val890fs frameshift NM_001406824.1:c.3275_3276dup NP_001393753.1:p.Val1093fs frameshift NM_001406825.1:c.3275_3276dup NP_001393754.1:p.Val1093fs frameshift NM_001406826.1:c.3404_3405dup NP_001393755.1:p.Val1136fs frameshift NM_001406827.1:c.3275_3276dup NP_001393756.1:p.Val1093fs frameshift NM_001406828.1:c.3275_3276dup NP_001393757.1:p.Val1093fs frameshift NM_001406829.1:c.2666_2667dup NP_001393758.1:p.Val890fs frameshift NM_001406830.1:c.3275_3276dup NP_001393759.1:p.Val1093fs frameshift NM_001406831.1:c.353_354dup NP_001393760.1:p.Val119fs frameshift NM_001406832.1:c.419_420dup NP_001393761.1:p.Val141fs frameshift NM_001407362.1:c.1517_1518dup NP_001394291.1:p.Val507fs frameshift NR_176256.1:n.2502_2503dup non-coding transcript variant NR_176257.1:n.3833_3834dup non-coding transcript variant NR_176258.1:n.3762_3763dup non-coding transcript variant NR_176259.1:n.3661_3662dup non-coding transcript variant NR_176260.1:n.1606_1607dup NR_176261.1:n.3543_3544dup non-coding transcript variant NC_000002.12:g.47805633_47805634dup NC_000002.11:g.48032772_48032773dup NG_007111.1:g.27487_27488dup NG_008397.1:g.105046_105047dup LRG_219:g.27487_27488dup LRG_219t1:c.3572_3573dup LRG_219p1:p.Val1192Leufs - Protein change
- V1017fs, V1062fs, V1093fs, V1134fs, V1136fs, V1166fs, V1192fs, V1194fs, V119fs, V1224fs, V141fs, V507fs, V670fs, V890fs, V904fs
- Other names
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- Canonical SPDI
- NC_000002.12:47805628:TTTTTT:TTTTTTTT
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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 22, 2024 | RCV004520710.1 |
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
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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
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 22, 2024)
|
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: SCV005033367.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.3572_3573dupTT pathogenic mutation, located in coding exon 7 of the MSH6 gene, results from a duplication of TT at nucleotide position 3572, causing a … (more)
The c.3572_3573dupTT pathogenic mutation, located in coding exon 7 of the MSH6 gene, results from a duplication of TT at nucleotide position 3572, causing a translational frameshift with a predicted alternate stop codon (p.V1192Lfs*4). 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.3572_3573dupTT pathogenic mutation, located in coding exon 7 of the MSH6 gene, results from a duplication of TT at nucleotide position 3572, causing a translational frameshift with a predicted alternate stop codon (p.V1192Lfs*4). 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 08, 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.