This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.1010dup (p.Leu337fs)
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/Likely 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
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NM_000179.3(MSH6):c.1010dup (p.Leu337fs)
Variation ID: 2673724 Accession: VCV002673724.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47798990-47798991 (GRCh38) [ NCBI UCSC ] 2: 48026129-48026130 (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 Dec 25, 2023 Dec 30, 2023 Aug 11, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.1010dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Leu337fs frameshift NM_001281492.2:c.620dup NP_001268421.1:p.Leu207fs frameshift NM_001281493.2:c.104dup NP_001268422.1:p.Leu35fs frameshift NM_001281494.2:c.104dup NP_001268423.1:p.Leu35fs frameshift NM_001406795.1:c.1106dup NP_001393724.1:p.Leu369fs frameshift NM_001406796.1:c.1010dup NP_001393725.1:p.Leu337fs frameshift NM_001406797.1:c.713dup NP_001393726.1:p.Leu238fs frameshift NM_001406798.1:c.1010dup NP_001393727.1:p.Leu337fs frameshift NM_001406799.1:c.485dup NP_001393728.1:p.Leu162fs frameshift NM_001406800.1:c.1010dup NP_001393729.1:p.Leu337fs frameshift NM_001406801.1:c.713dup NP_001393730.1:p.Leu238fs frameshift NM_001406802.1:c.1106dup NP_001393731.1:p.Leu369fs frameshift NM_001406803.1:c.1010dup NP_001393732.1:p.Leu337fs frameshift NM_001406804.1:c.932dup NP_001393733.1:p.Leu311fs frameshift NM_001406805.1:c.713dup NP_001393734.1:p.Leu238fs frameshift NM_001406806.1:c.485dup NP_001393735.1:p.Leu162fs frameshift NM_001406807.1:c.485dup NP_001393736.1:p.Leu162fs frameshift NM_001406808.1:c.1010dup NP_001393737.1:p.Leu337fs frameshift NM_001406809.1:c.1010dup NP_001393738.1:p.Leu337fs frameshift NM_001406811.1:c.104dup NP_001393740.1:p.Leu35fs frameshift NM_001406812.1:c.104dup NP_001393741.1:p.Leu35fs frameshift NM_001406813.1:c.1016dup NP_001393742.1:p.Leu339fs frameshift NM_001406814.1:c.104dup NP_001393743.1:p.Leu35fs frameshift NM_001406815.1:c.104dup NP_001393744.1:p.Leu35fs frameshift NM_001406816.1:c.104dup NP_001393745.1:p.Leu35fs frameshift NM_001406817.1:c.1010dup NP_001393746.1:p.Leu337fs frameshift NM_001406818.1:c.713dup NP_001393747.1:p.Leu238fs frameshift NM_001406819.1:c.713dup NP_001393748.1:p.Leu238fs frameshift NM_001406820.1:c.713dup NP_001393749.1:p.Leu238fs frameshift NM_001406821.1:c.713dup NP_001393750.1:p.Leu238fs frameshift NM_001406822.1:c.713dup NP_001393751.1:p.Leu238fs frameshift NM_001406823.1:c.104dup NP_001393752.1:p.Leu35fs frameshift NM_001406824.1:c.713dup NP_001393753.1:p.Leu238fs frameshift NM_001406825.1:c.713dup NP_001393754.1:p.Leu238fs frameshift NM_001406826.1:c.842dup NP_001393755.1:p.Leu281fs frameshift NM_001406827.1:c.713dup NP_001393756.1:p.Leu238fs frameshift NM_001406828.1:c.713dup NP_001393757.1:p.Leu238fs frameshift NM_001406829.1:c.104dup NP_001393758.1:p.Leu35fs frameshift NM_001406830.1:c.713dup NP_001393759.1:p.Leu238fs frameshift NM_001407362.1:c.628-1673dup intron variant NR_176257.1:n.1099dup non-coding transcript variant NR_176258.1:n.1099dup non-coding transcript variant NR_176259.1:n.1099dup non-coding transcript variant NR_176261.1:n.1099dup non-coding transcript variant NC_000002.12:g.47798993dup NC_000002.11:g.48026132dup NG_007111.1:g.20847dup LRG_219:g.20847dup LRG_219t1:c.1010dup LRG_219p1:p.Leu337Phefs - Protein change
- L162fs, L207fs, L238fs, L281fs, L311fs, L337fs, L339fs, L35fs, L369fs
- Other names
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- Canonical SPDI
- NC_000002.12:47798990:TTT:TTTT
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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 |
9159 | 9475 | |
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
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Aug 11, 2023 | RCV003450361.1 | |
| Likely pathogenic (1) |
criteria provided, single submitter
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May 5, 2022 | RCV003459871.1 |
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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Pathogenic
(Aug 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004187233.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Likely pathogenic
(May 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Endometrial carcinoma
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004198156.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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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 variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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 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.