This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2830del (p.Asp943_Ile944insTer)
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.
(2)
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.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000179.3(MSH6):c.2830del (p.Asp943_Ile944insTer)
Variation ID: 2673773 Accession: VCV002673773.2
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 2p16.3 2: 47800813 (GRCh38) [ NCBI UCSC ] 2: 48027952 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Dec 25, 2023 Feb 20, 2024 Sep 25, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.2830del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Asp943_Ile944insTer nonsense NM_001281492.2:c.2440del NP_001268421.1:p.Asp813_Ile814insTer nonsense NM_001281493.2:c.1924del NP_001268422.1:p.Asp641_Ile642insTer nonsense NM_001281494.2:c.1924del NP_001268423.1:p.Asp641_Ile642insTer nonsense NM_001406795.1:c.2926del NP_001393724.1:p.Asp975_Ile976insTer nonsense NM_001406796.1:c.2830del NP_001393725.1:p.Asp943_Ile944insTer nonsense NM_001406797.1:c.2533del NP_001393726.1:p.Asp844_Ile845insTer nonsense NM_001406798.1:c.2830del NP_001393727.1:p.Asp943_Ile944insTer nonsense NM_001406799.1:c.2305del NP_001393728.1:p.Asp768_Ile769insTer nonsense NM_001406800.1:c.2830del NP_001393729.1:p.Asp943_Ile944insTer nonsense NM_001406801.1:c.2533del NP_001393730.1:p.Asp844_Ile845insTer nonsense NM_001406802.1:c.2926del NP_001393731.1:p.Asp975_Ile976insTer nonsense NM_001406803.1:c.2308+522del intron variant NM_001406804.1:c.2752del NP_001393733.1:p.Asp917_Ile918insTer nonsense NM_001406805.1:c.2533del NP_001393734.1:p.Asp844_Ile845insTer nonsense NM_001406806.1:c.2305del NP_001393735.1:p.Asp768_Ile769insTer nonsense NM_001406807.1:c.2305del NP_001393736.1:p.Asp768_Ile769insTer nonsense NM_001406808.1:c.2830del NP_001393737.1:p.Asp943_Ile944insTer nonsense NM_001406809.1:c.2830del NP_001393738.1:p.Asp943_Ile944insTer nonsense NM_001406811.1:c.1924del NP_001393740.1:p.Asp641_Ile642insTer nonsense NM_001406812.1:c.1924del NP_001393741.1:p.Asp641_Ile642insTer nonsense NM_001406813.1:c.2836del NP_001393742.1:p.Asp945_Ile946insTer nonsense NM_001406814.1:c.1924del NP_001393743.1:p.Asp641_Ile642insTer nonsense NM_001406815.1:c.1924del NP_001393744.1:p.Asp641_Ile642insTer nonsense NM_001406816.1:c.1924del NP_001393745.1:p.Asp641_Ile642insTer nonsense NM_001406817.1:c.1606+1224del intron variant NM_001406818.1:c.2533del NP_001393747.1:p.Asp844_Ile845insTer nonsense NM_001406819.1:c.2533del NP_001393748.1:p.Asp844_Ile845insTer nonsense NM_001406820.1:c.2533del NP_001393749.1:p.Asp844_Ile845insTer nonsense NM_001406821.1:c.2533del NP_001393750.1:p.Asp844_Ile845insTer nonsense NM_001406822.1:c.2533del NP_001393751.1:p.Asp844_Ile845insTer nonsense NM_001406823.1:c.1924del NP_001393752.1:p.Asp641_Ile642insTer nonsense NM_001406824.1:c.2533del NP_001393753.1:p.Asp844_Ile845insTer nonsense NM_001406825.1:c.2533del NP_001393754.1:p.Asp844_Ile845insTer nonsense NM_001406826.1:c.2662del NP_001393755.1:p.Asp887_Ile888insTer nonsense NM_001406827.1:c.2533del NP_001393756.1:p.Asp844_Ile845insTer nonsense NM_001406828.1:c.2533del NP_001393757.1:p.Asp844_Ile845insTer nonsense NM_001406829.1:c.1924del NP_001393758.1:p.Asp641_Ile642insTer nonsense NM_001406830.1:c.2533del NP_001393759.1:p.Asp844_Ile845insTer nonsense NM_001407362.1:c.775del NP_001394291.1:p.Asp258_Ile259insTer nonsense NR_176256.1:n.1692del non-coding transcript variant NR_176257.1:n.2919del non-coding transcript variant NR_176258.1:n.2919del non-coding transcript variant NR_176259.1:n.2919del non-coding transcript variant NR_176260.1:n.864delA NR_176261.1:n.2919del non-coding transcript variant NC_000002.12:g.47800813del NC_000002.11:g.48027952del NG_007111.1:g.22667del LRG_219:g.22667del LRG_219t1:c.2830del LRG_219p1:p.Ile944Terfs - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000002.12:47800812:A:
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
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 |
9166 | 9485 | |
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
|
Sep 25, 2023 | RCV003450410.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 27, 2023 | RCV003759859.2 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Sep 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004187378.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
|
|
|
Pathogenic
(Feb 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004499955.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ile944*) in the MSH6 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ile944*) 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). 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. For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Ile944*) 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). 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. For these reasons, this variant has been classified as Pathogenic.
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 is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Comment:
This sequence change creates a premature translational stop signal (p.Ile944*) 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). 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. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 Oct 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.