This variant causes an in-frame insertion of six amino acids of the MSH6 protein. This variant occurs in the ATPase domain (PMID: 9564049, 10636912, 22232658) and MSH2 binding (PMID: 9774676). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.3985_3988delinsAATTTTGAGAAGATGAAGT (p.Ser1329delinsAsnPheGluLysMetLys)
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)
Help
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.
Uncertain significance
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.3985_3988delinsAATTTTGAGAAGATGAAGT (p.Ser1329delinsAsnPheGluLysMetLys)
Variation ID: 2773672 Accession: VCV002773672.1
- Type and length
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Indel, 19 bp
- Location
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Cytogenetic: 2p16.3 2: 47806635-47806638 (GRCh38) [ NCBI UCSC ] 2: 48033774-48033777 (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 Feb 14, 2024 Feb 14, 2024 Jun 13, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.3985_3988delinsAATTTTGAGAAGATGAAGT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Ser1329delinsAsnPheGluLysMetLys inframe indel NM_001281492.2:c.3595_3598delinsAATTTTGAGAAGATGAAGT NP_001268421.1:p.Ser1199delinsAsnPheGluLysMetLys inframe indel NM_001281493.2:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001268422.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001281494.2:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001268423.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406795.1:c.4081_4084delinsAATTTTGAGAAGATGAAGT NP_001393724.1:p.Ser1361delinsAsnPheGluLysMetLys inframe indel NM_001406796.1:c.3985_3988delinsAATTTTGAGAAGATGAAGT NP_001393725.1:p.Ser1329delinsAsnPheGluLysMetLys inframe indel NM_001406797.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393726.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406798.1:c.3811_3814delinsAATTTTGAGAAGATGAAGT NP_001393727.1:p.Ser1271delinsAsnPheGluLysMetLys inframe indel NM_001406799.1:c.3460_3463delinsAATTTTGAGAAGATGAAGT NP_001393728.1:p.Ser1154delinsAsnPheGluLysMetLys inframe indel NM_001406800.1:c.*6_*9delinsAATTTTGAGAAGATGAAGT 3 prime UTR NM_001406801.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393730.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406802.1:c.3898-144_3898-141delinsAATTTTGAGAAGATGAAGT intron variant NM_001406803.1:c.3121_3124delinsAATTTTGAGAAGATGAAGT NP_001393732.1:p.Ser1041delinsAsnPheGluLysMetLys inframe indel NM_001406804.1:c.3907_3910delinsAATTTTGAGAAGATGAAGT NP_001393733.1:p.Ser1303delinsAsnPheGluLysMetLys inframe indel NM_001406805.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393734.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406806.1:c.3460_3463delinsAATTTTGAGAAGATGAAGT NP_001393735.1:p.Ser1154delinsAsnPheGluLysMetLys inframe indel NM_001406807.1:c.3460_3463delinsAATTTTGAGAAGATGAAGT NP_001393736.1:p.Ser1154delinsAsnPheGluLysMetLys inframe indel NM_001406808.1:c.3985_3988delinsAATTTTGAGAAGATGAAGT NP_001393737.1:p.Ser1329delinsAsnPheGluLysMetLys inframe indel NM_001406809.1:c.3985_3988delinsAATTTTGAGAAGATGAAGT NP_001393738.1:p.Ser1329delinsAsnPheGluLysMetLys inframe indel NM_001406811.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393740.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406812.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393741.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406813.1:c.3991_3994delinsAATTTTGAGAAGATGAAGT NP_001393742.1:p.Ser1331delinsAsnPheGluLysMetLys inframe indel NM_001406814.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393743.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406815.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393744.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406816.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393745.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406817.1:c.2419_2422delinsAATTTTGAGAAGATGAAGT NP_001393746.1:p.Ser807delinsAsnPheGluLysMetLys inframe indel NM_001406818.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393747.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406819.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393748.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406820.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393749.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406821.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393750.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406822.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393751.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406823.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393752.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406824.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393753.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406825.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393754.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406826.1:c.3817_3820delinsAATTTTGAGAAGATGAAGT NP_001393755.1:p.Ser1273delinsAsnPheGluLysMetLys inframe indel NM_001406827.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393756.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406828.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393757.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406829.1:c.3079_3082delinsAATTTTGAGAAGATGAAGT NP_001393758.1:p.Ser1027delinsAsnPheGluLysMetLys inframe indel NM_001406830.1:c.3688_3691delinsAATTTTGAGAAGATGAAGT NP_001393759.1:p.Ser1230delinsAsnPheGluLysMetLys inframe indel NM_001406831.1:c.766_769delinsAATTTTGAGAAGATGAAGT NP_001393760.1:p.Ser256delinsAsnPheGluLysMetLys inframe indel NM_001406832.1:c.832_835delinsAATTTTGAGAAGATGAAGT NP_001393761.1:p.Ser278delinsAsnPheGluLysMetLys inframe indel NM_001407362.1:c.1930_1933delinsAATTTTGAGAAGATGAAGT NP_001394291.1:p.Ser644delinsAsnPheGluLysMetLys inframe indel NR_176256.1:n.2915_2918delinsAATTTTGAGAAGATGAAGT non-coding transcript variant NR_176257.1:n.4246_4249delinsAATTTTGAGAAGATGAAGT non-coding transcript variant NR_176258.1:n.4175_4178delinsAATTTTGAGAAGATGAAGT non-coding transcript variant NR_176259.1:n.4074_4077delinsAATTTTGAGAAGATGAAGT non-coding transcript variant NR_176260.1:n.2019_2022delTCACinsAATTTTGAGAAGATGAAGT NR_176261.1:n.3956_3959delinsAATTTTGAGAAGATGAAGT non-coding transcript variant NC_000002.12:g.47806635_47806638delinsAATTTTGAGAAGATGAAGT NC_000002.11:g.48033774_48033777delinsAATTTTGAGAAGATGAAGT NG_007111.1:g.28489_28492delinsAATTTTGAGAAGATGAAGT NG_008397.1:g.104038_104041delinsACTTCATCTTCTCAAAATT LRG_219:g.28489_28492delinsAATTTTGAGAAGATGAAGT LRG_219t1:c.3985_3988delTCACinsAATTTTGAGAAGATGAAGT LRG_219p1:p.Ser1329delinsAsnPheGluLysMetLys - Protein change
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- Other names
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- Canonical SPDI
- NC_000002.12:47806634:TCAC:AATTTTGAGAAGATGAAGT
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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. |
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| Uncertain significance (1) |
criteria provided, single submitter
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Jun 13, 2023 | RCV003585645.1 |
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
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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Uncertain significance
(Jun 13, 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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Color Diagnostics, LLC DBA Color Health
Accession: SCV004357779.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This variant causes an in-frame insertion of six amino acids of the MSH6 protein. This variant occurs in the ATPase domain (PMID: 9564049, 10636912, 22232658) … (more)
This variant causes an in-frame insertion of six amino acids of the MSH6 protein. This variant occurs in the ATPase domain (PMID: 9564049, 10636912, 22232658) and MSH2 binding (PMID: 9774676). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (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:
This variant causes an in-frame insertion of six amino acids of the MSH6 protein. This variant occurs in the ATPase domain (PMID: 9564049, 10636912, 22232658) and MSH2 binding (PMID: 9774676). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Interplay between mismatch repair and chromatin assembly. | Schöpf B | Proceedings of the National Academy of Sciences of the United States of America | 2012 | PMID: 22232658 |
| Mutation in the magnesium binding site of hMSH6 disables the hMutSalpha sliding clamp from translocating along DNA. | Iaccarino I | The Journal of biological chemistry | 2000 | PMID: 10636912 |
| Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer. | Guerrette S | Molecular and cellular biology | 1998 | PMID: 9774676 |
| hMSH2 and hMSH6 play distinct roles in mismatch binding and contribute differently to the ATPase activity of hMutSalpha. | Iaccarino I | The EMBO journal | 1998 | PMID: 9564049 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 20, 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.