ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.3850_3851dup (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_3851dup (p.Phe1285fs)
Variation ID: 2034592 Accession: VCV002034592.2
- Type and length
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Duplication, 2 bp
- Location
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Cytogenetic: 2p16.3 2: 47806499-47806500 (GRCh38) [ NCBI UCSC ] 2: 48033638-48033639 (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 Oct 7, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.3850_3851dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Phe1285fs frameshift NM_001281492.2:c.3460_3461dup NP_001268421.1:p.Phe1155fs frameshift NM_001281493.2:c.2944_2945dup NP_001268422.1:p.Phe983fs frameshift NM_001281494.2:c.2944_2945dup NP_001268423.1:p.Phe983fs frameshift NM_001406795.1:c.3946_3947dup NP_001393724.1:p.Phe1317Argfs frameshift NM_001406796.1:c.3850_3851dup NP_001393725.1:p.Phe1285Argfs frameshift NM_001406797.1:c.3553_3554dup NP_001393726.1:p.Phe1186Argfs frameshift NM_001406798.1:c.3676_3677dup NP_001393727.1:p.Phe1227Argfs frameshift NM_001406799.1:c.3325_3326dup NP_001393728.1:p.Phe1110Argfs frameshift NM_001406800.1:c.3837_3838dup NP_001393729.1:p.Arg1280Hisfs frameshift NM_001406801.1:c.3553_3554dup NP_001393730.1:p.Phe1186Argfs frameshift NM_001406803.1:c.2986_2987dup NP_001393732.1:p.Phe997Argfs frameshift NM_001406804.1:c.3772_3773dup NP_001393733.1:p.Phe1259Argfs frameshift NM_001406805.1:c.3553_3554dup NP_001393734.1:p.Phe1186Argfs frameshift NM_001406806.1:c.3325_3326dup NP_001393735.1:p.Phe1110Argfs frameshift NM_001406807.1:c.3325_3326dup NP_001393736.1:p.Phe1110Argfs frameshift NM_001406808.1:c.3850_3851dup NP_001393737.1:p.Phe1285Argfs frameshift NM_001406809.1:c.3850_3851dup NP_001393738.1:p.Phe1285Argfs frameshift NM_001406811.1:c.2944_2945dup NP_001393740.1:p.Phe983Argfs frameshift NM_001406812.1:c.2944_2945dup NP_001393741.1:p.Phe983Argfs frameshift NM_001406813.1:c.3856_3857dup NP_001393742.1:p.Phe1287Argfs frameshift NM_001406814.1:c.2944_2945dup NP_001393743.1:p.Phe983Argfs frameshift NM_001406815.1:c.2944_2945dup NP_001393744.1:p.Phe983Argfs frameshift NM_001406816.1:c.2944_2945dup NP_001393745.1:p.Phe983Argfs frameshift NM_001406817.1:c.2284_2285dup NP_001393746.1:p.Phe763Argfs frameshift NM_001406818.1:c.3553_3554dup NP_001393747.1:p.Phe1186Argfs frameshift NM_001406819.1:c.3553_3554dup NP_001393748.1:p.Phe1186Argfs frameshift NM_001406820.1:c.3553_3554dup NP_001393749.1:p.Phe1186Argfs frameshift NM_001406821.1:c.3553_3554dup NP_001393750.1:p.Phe1186Argfs frameshift NM_001406822.1:c.3553_3554dup NP_001393751.1:p.Phe1186Argfs frameshift NM_001406823.1:c.2944_2945dup NP_001393752.1:p.Phe983Argfs frameshift NM_001406824.1:c.3553_3554dup NP_001393753.1:p.Phe1186Argfs frameshift NM_001406825.1:c.3553_3554dup NP_001393754.1:p.Phe1186Argfs frameshift NM_001406826.1:c.3682_3683dup NP_001393755.1:p.Phe1229Argfs frameshift NM_001406827.1:c.3553_3554dup NP_001393756.1:p.Phe1186Argfs frameshift NM_001406828.1:c.3553_3554dup NP_001393757.1:p.Phe1186Argfs frameshift NM_001406829.1:c.2944_2945dup NP_001393758.1:p.Phe983Argfs frameshift NM_001406830.1:c.3553_3554dup NP_001393759.1:p.Phe1186Argfs frameshift NM_001406831.1:c.631_632dup NP_001393760.1:p.Phe212Argfs frameshift NM_001406832.1:c.697_698dup NP_001393761.1:p.Phe234Argfs frameshift NM_001407362.1:c.1795_1796dup NP_001394291.1:p.Phe600Argfs frameshift NR_176256.1:n.2780_2781dup NR_176257.1:n.4111_4112dup NR_176258.1:n.4040_4041dup NR_176259.1:n.3939_3940dup NR_176260.1:n.1884_1885dup NR_176261.1:n.3821_3822dup NC_000002.12:g.47806500_47806501dup NC_000002.11:g.48033639_48033640dup NG_007111.1:g.28354_28355dup NG_008397.1:g.104175_104176dup LRG_219:g.28354_28355dup LRG_219t1:c.3850_3851dup LRG_219p1:p.Phe1285Argfs - Protein change
- F1155fs, F983fs, F1285fs
- Other names
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- Canonical SPDI
- NC_000002.12:47806499:AC:ACAC
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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Oct 7, 2022 | RCV002889673.2 |
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
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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
(Oct 07, 2022)
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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: SCV003235964.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MSH6 protein in which other variant(s) (p.Arg1331*) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MSH6 protein in which other variant(s) (p.Arg1331*) have been determined to be pathogenic (PMID: 16034045, 16418736, 18301448, 19851887, 20587412, 21056691, 21155762, 21642682, 27601186). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.Phe1285Argfs*43) in the MSH6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the MSH6 protein. (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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Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population. | Lagerstedt-Robinson K | Oncology reports | 2016 | PMID: 27601186 |
Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. | Bonadona V | JAMA | 2011 | PMID: 21642682 |
Characterization of two Ashkenazi Jewish founder mutations in MSH6 gene causing Lynch syndrome. | Raskin L | Clinical genetics | 2011 | PMID: 21155762 |
Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer. | Limburg PJ | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2011 | PMID: 21056691 |
Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. | Sjursen W | Journal of medical genetics | 2010 | PMID: 20587412 |
An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC. | Goldberg Y | Familial cancer | 2010 | PMID: 19851887 |
No association between MUTYH and MSH6 germline mutations in 64 HNPCC patients. | Steinke V | European journal of human genetics : EJHG | 2008 | PMID: 18301448 |
Compound heterozygosity for two MSH6 mutations in a patient with early onset of HNPCC-associated cancers, but without hematological malignancy and brain tumor. | Plaschke J | European journal of human genetics : EJHG | 2006 | PMID: 16418736 |
Immunohistochemistry identifies carriers of mismatch repair gene defects causing hereditary nonpolyposis colorectal cancer. | Stormorken AT | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2005 | PMID: 16034045 |
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.