This sequence change results in a frameshift in the MSH6 gene (p.Lys1358Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the MSH6 protein and extend the protein by 11 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.4068_4072dup (p.Lys1358fs)
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.4068_4072dup (p.Lys1358fs)
Variation ID: 1992733 Accession: VCV001992733.2
- Type and length
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Duplication, 5 bp
- Location
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Cytogenetic: 2p16.3 2: 47806844-47806845 (GRCh38) [ NCBI UCSC ] 2: 48033983-48033984 (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 8, 2023 Feb 20, 2024 May 10, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.4068_4072dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Lys1358fs frameshift NM_001281492.2:c.3678_3682dup NP_001268421.1:p.Lys1228fs frameshift NM_001281493.2:c.3162_3166dup NP_001268422.1:p.Lys1056fs frameshift NM_001281494.2:c.3162_3166dup NP_001268423.1:p.Lys1056fs frameshift NM_001406795.1:c.4164_4168dup NP_001393724.1:p.Lys1390Argfs frameshift NM_001406796.1:c.4068_4072dup NP_001393725.1:p.Lys1358Argfs frameshift NM_001406797.1:c.3771_3775dup NP_001393726.1:p.Lys1259Argfs frameshift NM_001406798.1:c.3894_3898dup NP_001393727.1:p.Lys1300Argfs frameshift NM_001406799.1:c.3543_3547dup NP_001393728.1:p.Lys1183Argfs frameshift NM_001406800.1:c.*89_*93dup NM_001406801.1:c.*49_*53dup NM_001406802.1:c.*49_*53dup NM_001406803.1:c.3204_3208dup NP_001393732.1:p.Lys1070Argfs frameshift NM_001406804.1:c.3990_3994dup NP_001393733.1:p.Lys1332Argfs frameshift NM_001406805.1:c.3771_3775dup NP_001393734.1:p.Lys1259Argfs frameshift NM_001406806.1:c.3543_3547dup NP_001393735.1:p.Lys1183Argfs frameshift NM_001406807.1:c.3543_3547dup NP_001393736.1:p.Lys1183Argfs frameshift NM_001406808.1:c.*49_*53dup NM_001406809.1:c.4068_4072dup NP_001393738.1:p.Lys1358Argfs frameshift NM_001406811.1:c.3162_3166dup NP_001393740.1:p.Lys1056Argfs frameshift NM_001406812.1:c.3162_3166dup NP_001393741.1:p.Lys1056Argfs frameshift NM_001406813.1:c.4074_4078dup NP_001393742.1:p.Lys1360Argfs frameshift NM_001406814.1:c.3162_3166dup NP_001393743.1:p.Lys1056Argfs frameshift NM_001406815.1:c.3162_3166dup NP_001393744.1:p.Lys1056Argfs frameshift NM_001406816.1:c.3162_3166dup NP_001393745.1:p.Lys1056Argfs frameshift NM_001406817.1:c.2502_2506dup NP_001393746.1:p.Lys836Argfs frameshift NM_001406818.1:c.3771_3775dup NP_001393747.1:p.Lys1259Argfs frameshift NM_001406819.1:c.3771_3775dup NP_001393748.1:p.Lys1259Argfs frameshift NM_001406820.1:c.3771_3775dup NP_001393749.1:p.Lys1259Argfs frameshift NM_001406821.1:c.3771_3775dup NP_001393750.1:p.Lys1259Argfs frameshift NM_001406822.1:c.*49_*53dup NM_001406823.1:c.3162_3166dup NP_001393752.1:p.Lys1056Argfs frameshift NM_001406824.1:c.3771_3775dup NP_001393753.1:p.Lys1259Argfs frameshift NM_001406825.1:c.3771_3775dup NP_001393754.1:p.Lys1259Argfs frameshift NM_001406826.1:c.3900_3904dup NP_001393755.1:p.Lys1302Argfs frameshift NM_001406827.1:c.3771_3775dup NP_001393756.1:p.Lys1259Argfs frameshift NM_001406828.1:c.3771_3775dup NP_001393757.1:p.Lys1259Argfs frameshift NM_001406829.1:c.3162_3166dup NP_001393758.1:p.Lys1056Argfs frameshift NM_001406830.1:c.3771_3775dup NP_001393759.1:p.Lys1259Argfs frameshift NM_001406831.1:c.849_853dup NP_001393760.1:p.Lys285Argfs frameshift NM_001406832.1:c.915_919dup NP_001393761.1:p.Lys307Argfs frameshift NM_001407362.1:c.2013_2017dup NP_001394291.1:p.Lys673Argfs frameshift NR_176256.1:n.2998_3002dup NR_176257.1:n.4329_4333dup NR_176258.1:n.4258_4262dup NR_176259.1:n.4157_4161dup NR_176260.1:n.2102_2106dup NR_176261.1:n.4039_4043dup NC_000002.12:g.47806845_47806849dup NC_000002.11:g.48033984_48033988dup NG_007111.1:g.28699_28703dup NG_008397.1:g.103827_103831dup LRG_219:g.28699_28703dup LRG_219t1:c.4068_4072dup LRG_219p1:p.Lys1358Argfs - Protein change
- K1228fs, K1056fs, K1358fs
- Other names
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- Canonical SPDI
- NC_000002.12:47806844:GATTA:GATTAGATTA
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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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
May 10, 2022 | RCV002796146.3 |
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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|---|---|---|---|---|---|
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Uncertain significance
(May 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003201683.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change results in a frameshift in the MSH6 gene (p.Lys1358Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is … (more)
This sequence change results in a frameshift in the MSH6 gene (p.Lys1358Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the MSH6 protein and extend the protein by 11 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. (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 sequence change results in a frameshift in the MSH6 gene (p.Lys1358Argfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the MSH6 protein and extend the protein by 11 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
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 29, 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.