ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.3850_3853dup (p.Phe1285fs)
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.3850_3853dup (p.Phe1285fs)
Variation ID: 1735519 Accession: VCV001735519.5
- Type and length
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Duplication, 4 bp
- Location
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Cytogenetic: 2p16.3 2: 47806498-47806499 (GRCh38) [ NCBI UCSC ] 2: 48033637-48033638 (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 Aug 11, 2024 Jun 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.3850_3853dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Phe1285fs frameshift NM_000179.2:c.3850_3853dupACGT frameshift NM_001281492.2:c.3460_3463dup NP_001268421.1:p.Phe1155fs frameshift NM_001281493.2:c.2944_2947dup NP_001268422.1:p.Phe983fs frameshift NM_001281494.2:c.2944_2947dup NP_001268423.1:p.Phe983fs frameshift NM_001406795.1:c.3946_3949dup NP_001393724.1:p.Phe1317Tyrfs frameshift NM_001406796.1:c.3850_3853dup NP_001393725.1:p.Phe1285Tyrfs frameshift NM_001406797.1:c.3553_3556dup NP_001393726.1:p.Phe1186Tyrfs frameshift NM_001406798.1:c.3676_3679dup NP_001393727.1:p.Phe1227Tyrfs frameshift NM_001406799.1:c.3325_3328dup NP_001393728.1:p.Phe1110Tyrfs frameshift NM_001406800.1:c.3837_3840dup NP_001393729.1:p.Ser1281Thrfs frameshift NM_001406801.1:c.3553_3556dup NP_001393730.1:p.Phe1186Tyrfs frameshift NM_001406803.1:c.2986_2989dup NP_001393732.1:p.Phe997Tyrfs frameshift NM_001406804.1:c.3772_3775dup NP_001393733.1:p.Phe1259Tyrfs frameshift NM_001406805.1:c.3553_3556dup NP_001393734.1:p.Phe1186Tyrfs frameshift NM_001406806.1:c.3325_3328dup NP_001393735.1:p.Phe1110Tyrfs frameshift NM_001406807.1:c.3325_3328dup NP_001393736.1:p.Phe1110Tyrfs frameshift NM_001406808.1:c.3850_3853dup NP_001393737.1:p.Phe1285Tyrfs frameshift NM_001406809.1:c.3850_3853dup NP_001393738.1:p.Phe1285Tyrfs frameshift NM_001406811.1:c.2944_2947dup NP_001393740.1:p.Phe983Tyrfs frameshift NM_001406812.1:c.2944_2947dup NP_001393741.1:p.Phe983Tyrfs frameshift NM_001406813.1:c.3856_3859dup NP_001393742.1:p.Phe1287Tyrfs frameshift NM_001406814.1:c.2944_2947dup NP_001393743.1:p.Phe983Tyrfs frameshift NM_001406815.1:c.2944_2947dup NP_001393744.1:p.Phe983Tyrfs frameshift NM_001406816.1:c.2944_2947dup NP_001393745.1:p.Phe983Tyrfs frameshift NM_001406817.1:c.2284_2287dup NP_001393746.1:p.Phe763Tyrfs frameshift NM_001406818.1:c.3553_3556dup NP_001393747.1:p.Phe1186Tyrfs frameshift NM_001406819.1:c.3553_3556dup NP_001393748.1:p.Phe1186Tyrfs frameshift NM_001406820.1:c.3553_3556dup NP_001393749.1:p.Phe1186Tyrfs frameshift NM_001406821.1:c.3553_3556dup NP_001393750.1:p.Phe1186Tyrfs frameshift NM_001406822.1:c.3553_3556dup NP_001393751.1:p.Phe1186Tyrfs frameshift NM_001406823.1:c.2944_2947dup NP_001393752.1:p.Phe983Tyrfs frameshift NM_001406824.1:c.3553_3556dup NP_001393753.1:p.Phe1186Tyrfs frameshift NM_001406825.1:c.3553_3556dup NP_001393754.1:p.Phe1186Tyrfs frameshift NM_001406826.1:c.3682_3685dup NP_001393755.1:p.Phe1229Tyrfs frameshift NM_001406827.1:c.3553_3556dup NP_001393756.1:p.Phe1186Tyrfs frameshift NM_001406828.1:c.3553_3556dup NP_001393757.1:p.Phe1186Tyrfs frameshift NM_001406829.1:c.2944_2947dup NP_001393758.1:p.Phe983Tyrfs frameshift NM_001406830.1:c.3553_3556dup NP_001393759.1:p.Phe1186Tyrfs frameshift NM_001406831.1:c.631_634dup NP_001393760.1:p.Phe212Tyrfs frameshift NM_001406832.1:c.697_700dup NP_001393761.1:p.Phe234Tyrfs frameshift NM_001407362.1:c.1795_1798dup NP_001394291.1:p.Phe600Tyrfs frameshift NR_176256.1:n.2780_2783dup NR_176257.1:n.4111_4114dup NR_176258.1:n.4040_4043dup NR_176259.1:n.3939_3942dup NR_176260.1:n.1884_1887dup NR_176261.1:n.3821_3824dup NC_000002.12:g.47806500_47806503dup NC_000002.11:g.48033639_48033642dup NG_007111.1:g.28354_28357dup NG_008397.1:g.104174_104177dup LRG_219:g.28354_28357dup LRG_219t1:c.3850_3853dup LRG_219p1:p.Phe1285Tyrfs - Protein change
- F1285fs, F1155fs, F983fs
- Other names
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- Canonical SPDI
- NC_000002.12:47806498:TACGT:TACGTACGT
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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
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 |
9149 | 9460 |
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
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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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Jun 19, 2024 | RCV002355482.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 25, 2023 | RCV003454140.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 15, 2023 | RCV003759117.1 |
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
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
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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
(Aug 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004187103.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(Jan 15, 2023)
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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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Invitae
Accession: SCV004426039.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This variant has not been reported in the literature in individuals affected with MSH6-related conditions. For these reasons, this variant has been classified as Pathogenic. … (more)
This variant has not been reported in the literature in individuals affected with MSH6-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1735519). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1285Tyrfs*5) 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). (less)
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Pathogenic
(Jun 19, 2024)
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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: SCV002621503.3
First in ClinVar: Nov 29, 2022 Last updated: Aug 11, 2024 |
Comment:
The c.3850_3853dupACGT pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of ACGT at nucleotide position 3850, causing a … (more)
The c.3850_3853dupACGT pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of ACGT at nucleotide position 3850, causing a translational frameshift with a predicted alternate stop codon (p.F1285Yfs*5). 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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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 Aug 11, 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.