ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.1960_1961del (p.Met654fs)
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.1960_1961del (p.Met654fs)
Variation ID: 1783417 Accession: VCV001783417.2
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 2p16.3 2: 47799943-47799944 (GRCh38) [ NCBI UCSC ] 2: 48027082-48027083 (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 25, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.1960_1961del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Met654fs frameshift NM_001281492.2:c.1570_1571del NP_001268421.1:p.Met524fs frameshift NM_001281493.2:c.1054_1055del NP_001268422.1:p.Met352fs frameshift NM_001281494.2:c.1054_1055del NP_001268423.1:p.Met352fs frameshift NM_001406795.1:c.2056_2057delAT NP_001393724.1:p.Met686Valfs frameshift NM_001406796.1:c.1960_1961delAT NP_001393725.1:p.Met654Valfs frameshift NM_001406797.1:c.1663_1664delAT NP_001393726.1:p.Met555Valfs frameshift NM_001406798.1:c.1960_1961delAT NP_001393727.1:p.Met654Valfs frameshift NM_001406799.1:c.1435_1436delAT NP_001393728.1:p.Met479Valfs frameshift NM_001406800.1:c.1960_1961delAT NP_001393729.1:p.Met654Valfs frameshift NM_001406801.1:c.1663_1664delAT NP_001393730.1:p.Met555Valfs frameshift NM_001406802.1:c.2056_2057delAT NP_001393731.1:p.Met686Valfs frameshift NM_001406803.1:c.1960_1961delAT NP_001393732.1:p.Met654Valfs frameshift NM_001406804.1:c.1882_1883delAT NP_001393733.1:p.Met628Valfs frameshift NM_001406805.1:c.1663_1664delAT NP_001393734.1:p.Met555Valfs frameshift NM_001406806.1:c.1435_1436delAT NP_001393735.1:p.Met479Valfs frameshift NM_001406807.1:c.1435_1436delAT NP_001393736.1:p.Met479Valfs frameshift NM_001406808.1:c.1960_1961delAT NP_001393737.1:p.Met654Valfs frameshift NM_001406809.1:c.1960_1961delAT NP_001393738.1:p.Met654Valfs frameshift NM_001406811.1:c.1054_1055delAT NP_001393740.1:p.Met352Valfs frameshift NM_001406812.1:c.1054_1055delAT NP_001393741.1:p.Met352Valfs frameshift NM_001406813.1:c.1966_1967delAT NP_001393742.1:p.Met656Valfs frameshift NM_001406814.1:c.1054_1055delAT NP_001393743.1:p.Met352Valfs frameshift NM_001406815.1:c.1054_1055delAT NP_001393744.1:p.Met352Valfs frameshift NM_001406816.1:c.1054_1055delAT NP_001393745.1:p.Met352Valfs frameshift NM_001406818.1:c.1663_1664delAT NP_001393747.1:p.Met555Valfs frameshift NM_001406819.1:c.1663_1664delAT NP_001393748.1:p.Met555Valfs frameshift NM_001406820.1:c.1663_1664delAT NP_001393749.1:p.Met555Valfs frameshift NM_001406821.1:c.1663_1664delAT NP_001393750.1:p.Met555Valfs frameshift NM_001406822.1:c.1663_1664delAT NP_001393751.1:p.Met555Valfs frameshift NM_001406823.1:c.1054_1055delAT NP_001393752.1:p.Met352Valfs frameshift NM_001406824.1:c.1663_1664delAT NP_001393753.1:p.Met555Valfs frameshift NM_001406825.1:c.1663_1664delAT NP_001393754.1:p.Met555Valfs frameshift NM_001406826.1:c.1792_1793delAT NP_001393755.1:p.Met598Valfs frameshift NM_001406827.1:c.1663_1664delAT NP_001393756.1:p.Met555Valfs frameshift NM_001406828.1:c.1663_1664delAT NP_001393757.1:p.Met555Valfs frameshift NM_001406829.1:c.1054_1055delAT NP_001393758.1:p.Met352Valfs frameshift NM_001406830.1:c.1663_1664delAT NP_001393759.1:p.Met555Valfs frameshift NR_176256.1:n.822_823delAT NR_176257.1:n.2049_2050delAT NR_176258.1:n.2049_2050delAT NR_176259.1:n.2049_2050delAT NR_176261.1:n.2049_2050delAT NC_000002.12:g.47799943_47799944del NC_000002.11:g.48027082_48027083del NG_007111.1:g.21797_21798del LRG_219:g.21797_21798del LRG_219t1:c.1960_1961del LRG_219p1:p.Met654Valfs - Protein change
- M352fs, M524fs, M654fs
- Other names
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- Canonical SPDI
- NC_000002.12:47799942:AT:
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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 |
9153 | 9466 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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 25, 2022 | RCV002421726.2 |
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
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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 25, 2022)
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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: SCV002721432.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1960_1961delAT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1960 to … (more)
The c.1960_1961delAT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1960 to 1961, causing a translational frameshift with a predicted alternate stop codon (p.M654Vfs*6). This variant has been identified as somatic in conjunction with a somatic pathogenic MSH6 variant in a tumor that demonstrated high microsatellite instability with loss of MSH6 expression by immunohistochemistry (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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
HelpThere 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 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.