ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.1298_1299del (p.Phe432_Tyr433insTer)
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.1298_1299del (p.Phe432_Tyr433insTer)
Variation ID: 1769254 Accession: VCV001769254.2
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 2p16.3 2: 47799280-47799281 (GRCh38) [ NCBI UCSC ] 2: 48026419-48026420 (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 Nov 29, 2022 May 1, 2024 Jul 9, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.1298_1299del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Phe432_Tyr433insTer nonsense NM_001281492.2:c.908_909del NP_001268421.1:p.Phe302_Tyr303insTer nonsense NM_001281493.2:c.392_393del NP_001268422.1:p.Phe130_Tyr131insTer nonsense NM_001281494.2:c.392_393del NP_001268423.1:p.Phe130_Tyr131insTer nonsense NM_001406795.1:c.1394_1395delAT NP_001393724.1:p.Tyr465Terfs frameshift nonsense NM_001406796.1:c.1298_1299delAT NP_001393725.1:p.Tyr433Terfs frameshift nonsense NM_001406797.1:c.1001_1002delAT NP_001393726.1:p.Tyr334Terfs frameshift nonsense NM_001406798.1:c.1298_1299delAT NP_001393727.1:p.Tyr433Terfs frameshift nonsense NM_001406799.1:c.773_774delAT NP_001393728.1:p.Tyr258Terfs frameshift nonsense NM_001406800.1:c.1298_1299delAT NP_001393729.1:p.Tyr433Terfs frameshift nonsense NM_001406801.1:c.1001_1002delAT NP_001393730.1:p.Tyr334Terfs frameshift nonsense NM_001406802.1:c.1394_1395delAT NP_001393731.1:p.Tyr465Terfs frameshift nonsense NM_001406803.1:c.1298_1299delAT NP_001393732.1:p.Tyr433Terfs frameshift nonsense NM_001406804.1:c.1220_1221delAT NP_001393733.1:p.Tyr407Terfs frameshift nonsense NM_001406805.1:c.1001_1002delAT NP_001393734.1:p.Tyr334Terfs frameshift nonsense NM_001406806.1:c.773_774delAT NP_001393735.1:p.Tyr258Terfs frameshift nonsense NM_001406807.1:c.773_774delAT NP_001393736.1:p.Tyr258Terfs frameshift nonsense NM_001406808.1:c.1298_1299delAT NP_001393737.1:p.Tyr433Terfs frameshift nonsense NM_001406809.1:c.1298_1299delAT NP_001393738.1:p.Tyr433Terfs frameshift nonsense NM_001406811.1:c.392_393delAT NP_001393740.1:p.Tyr131Terfs frameshift nonsense NM_001406812.1:c.392_393delAT NP_001393741.1:p.Tyr131Terfs frameshift nonsense NM_001406813.1:c.1304_1305delAT NP_001393742.1:p.Tyr435Terfs frameshift nonsense NM_001406814.1:c.392_393delAT NP_001393743.1:p.Tyr131Terfs frameshift nonsense NM_001406815.1:c.392_393delAT NP_001393744.1:p.Tyr131Terfs frameshift nonsense NM_001406816.1:c.392_393delAT NP_001393745.1:p.Tyr131Terfs frameshift nonsense NM_001406817.1:c.1298_1299delAT NP_001393746.1:p.Tyr433Terfs frameshift nonsense NM_001406818.1:c.1001_1002delAT NP_001393747.1:p.Tyr334Terfs frameshift nonsense NM_001406819.1:c.1001_1002delAT NP_001393748.1:p.Tyr334Terfs frameshift nonsense NM_001406820.1:c.1001_1002delAT NP_001393749.1:p.Tyr334Terfs frameshift nonsense NM_001406821.1:c.1001_1002delAT NP_001393750.1:p.Tyr334Terfs frameshift nonsense NM_001406822.1:c.1001_1002delAT NP_001393751.1:p.Tyr334Terfs frameshift nonsense NM_001406823.1:c.392_393delAT NP_001393752.1:p.Tyr131Terfs frameshift nonsense NM_001406824.1:c.1001_1002delAT NP_001393753.1:p.Tyr334Terfs frameshift nonsense NM_001406825.1:c.1001_1002delAT NP_001393754.1:p.Tyr334Terfs frameshift nonsense NM_001406826.1:c.1130_1131delAT NP_001393755.1:p.Tyr377Terfs frameshift nonsense NM_001406827.1:c.1001_1002delAT NP_001393756.1:p.Tyr334Terfs frameshift nonsense NM_001406828.1:c.1001_1002delAT NP_001393757.1:p.Tyr334Terfs frameshift nonsense NM_001406829.1:c.392_393delAT NP_001393758.1:p.Tyr131Terfs frameshift nonsense NM_001406830.1:c.1001_1002delAT NP_001393759.1:p.Tyr334Terfs frameshift nonsense NR_176257.1:n.1387_1388delAT NR_176258.1:n.1387_1388delAT NR_176259.1:n.1387_1388delAT NR_176261.1:n.1387_1388delAT NC_000002.12:g.47799281_47799282del NC_000002.11:g.48026420_48026421del NG_007111.1:g.21135_21136del LRG_219:g.21135_21136del LRG_219t1:c.1298_1299del LRG_219p1:p.Tyr433Terfs - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:47799279:TAT:T
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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
Help
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
Help
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 |
9157 | 9471 |
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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Jul 9, 2020 | RCV002380692.2 |
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
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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
(Jul 09, 2020)
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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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Ambry Genetics
Accession: SCV002695524.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1298_1299delAT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1298 to … (more)
The c.1298_1299delAT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1298 to 1299, causing a translational frameshift with a predicted alternate stop codon (p.Y433*). An alteration with a different nucleotide change leading to the same alternate stop codon (designated c.1299T>A, p.Tyr433X) has been reported in an individual diagnosed with rectal cancer in which tumor tissue showed loss of MSH6 protein staining on immunohistochemical testing (Julié C et al. Am. J. Gastroenterol., 2008 Nov;103:2825-35; quiz 2836). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (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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Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. | Julié C | The American journal of gastroenterology | 2008 | PMID: 18759827 |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.