In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val1345Asnfs*5) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the MSH6 protein.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.4029_4032dup (p.Val1345fs)
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
-
NM_000179.3(MSH6):c.4029_4032dup (p.Val1345fs)
Variation ID: 2847498 Accession: VCV002847498.1
- Type and length
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Duplication, 4 bp
- Location
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Cytogenetic: 2p16.3 2: 47806805-47806806 (GRCh38) [ NCBI UCSC ] 2: 48033944-48033945 (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 20, 2024 Feb 20, 2024 Mar 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.4029_4032dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Val1345fs frameshift NM_001281492.2:c.3639_3642dup NP_001268421.1:p.Val1215fs frameshift NM_001281493.2:c.3123_3126dup NP_001268422.1:p.Val1043fs frameshift NM_001281494.2:c.3123_3126dup NP_001268423.1:p.Val1043fs frameshift NM_001406795.1:c.4125_4128dup NP_001393724.1:p.Val1377fs frameshift NM_001406796.1:c.4029_4032dup NP_001393725.1:p.Val1345fs frameshift NM_001406797.1:c.3732_3735dup NP_001393726.1:p.Val1246fs frameshift NM_001406798.1:c.3855_3858dup NP_001393727.1:p.Val1287fs frameshift NM_001406799.1:c.3504_3507dup NP_001393728.1:p.Val1170fs frameshift NM_001406800.1:c.*50_*53dup 3 prime UTR NM_001406801.1:c.*10_*13dup 3 prime UTR NM_001406802.1:c.*10_*13dup 3 prime UTR NM_001406803.1:c.3165_3168dup NP_001393732.1:p.Val1057fs frameshift NM_001406804.1:c.3951_3954dup NP_001393733.1:p.Val1319fs frameshift NM_001406805.1:c.3732_3735dup NP_001393734.1:p.Val1246fs frameshift NM_001406806.1:c.3504_3507dup NP_001393735.1:p.Val1170fs frameshift NM_001406807.1:c.3504_3507dup NP_001393736.1:p.Val1170fs frameshift NM_001406808.1:c.*10_*13dup 3 prime UTR NM_001406809.1:c.4029_4032dup NP_001393738.1:p.Val1345fs frameshift NM_001406811.1:c.3123_3126dup NP_001393740.1:p.Val1043fs frameshift NM_001406812.1:c.3123_3126dup NP_001393741.1:p.Val1043fs frameshift NM_001406813.1:c.4035_4038dup NP_001393742.1:p.Val1347fs frameshift NM_001406814.1:c.3123_3126dup NP_001393743.1:p.Val1043fs frameshift NM_001406815.1:c.3123_3126dup NP_001393744.1:p.Val1043fs frameshift NM_001406816.1:c.3123_3126dup NP_001393745.1:p.Val1043fs frameshift NM_001406817.1:c.2463_2466dup NP_001393746.1:p.Val823fs frameshift NM_001406818.1:c.3732_3735dup NP_001393747.1:p.Val1246fs frameshift NM_001406819.1:c.3732_3735dup NP_001393748.1:p.Val1246fs frameshift NM_001406820.1:c.3732_3735dup NP_001393749.1:p.Val1246fs frameshift NM_001406821.1:c.3732_3735dup NP_001393750.1:p.Val1246fs frameshift NM_001406822.1:c.*10_*13dup 3 prime UTR NM_001406823.1:c.3123_3126dup NP_001393752.1:p.Val1043fs frameshift NM_001406824.1:c.3732_3735dup NP_001393753.1:p.Val1246fs frameshift NM_001406825.1:c.3732_3735dup NP_001393754.1:p.Val1246fs frameshift NM_001406826.1:c.3861_3864dup NP_001393755.1:p.Val1289fs frameshift NM_001406827.1:c.3732_3735dup NP_001393756.1:p.Val1246fs frameshift NM_001406828.1:c.3732_3735dup NP_001393757.1:p.Val1246fs frameshift NM_001406829.1:c.3123_3126dup NP_001393758.1:p.Val1043fs frameshift NM_001406830.1:c.3732_3735dup NP_001393759.1:p.Val1246fs frameshift NM_001406831.1:c.810_813dup NP_001393760.1:p.Val272fs frameshift NM_001406832.1:c.876_879dup NP_001393761.1:p.Val294fs frameshift NM_001407362.1:c.1974_1977dup NP_001394291.1:p.Val660fs frameshift NR_176256.1:n.2959_2962dup non-coding transcript variant NR_176257.1:n.4290_4293dup non-coding transcript variant NR_176258.1:n.4219_4222dup non-coding transcript variant NR_176259.1:n.4118_4121dup non-coding transcript variant NR_176260.1:n.2063_2066dup NR_176261.1:n.4000_4003dup non-coding transcript variant NC_000002.12:g.47806806_47806809dup NC_000002.11:g.48033945_48033948dup NG_007111.1:g.28660_28663dup NG_008397.1:g.103867_103870dup LRG_219:g.28660_28663dup LRG_219t1:c.4029_4032dup LRG_219p1:p.Val1345Asnfs - Protein change
- V1043fs, V1347fs, V1170fs, V1215fs, V1246fs, V294fs, V660fs, V1289fs, V1319fs, V1345fs, V272fs, V1057fs, V1287fs, V1377fs, V823fs
- Other names
- -
- Canonical SPDI
- NC_000002.12:47806805:AACT:AACTAACT
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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.
- -
- 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. |
|||
| 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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 19, 2023 | RCV003758536.2 |
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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Uncertain significance
(Mar 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004448658.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val1345Asnfs*5) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the MSH6 protein. (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:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val1345Asnfs*5) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the MSH6 protein.
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 Sep 30, 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.