In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 variant, c.2303_2305del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the MSH6 protein (p.Pro768_Phe769delinsLeu).
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2303_2305del (p.Pro768_Phe769delinsLeu)
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.
(1)
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.
Uncertain significance
1
criteria provided, single submitter
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.2303_2305del (p.Pro768_Phe769delinsLeu)
Variation ID: 2118668 Accession: VCV002118668.2
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: 2p16.3 2: 47800286-47800288 (GRCh38) [ NCBI UCSC ] 2: 48027425-48027427 (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 Mar 28, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.2303_2305del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Pro768_Phe769delinsLeu inframe indel NM_001281492.2:c.1913_1915del NP_001268421.1:p.Pro638_Phe639delinsLeu inframe indel NM_001281493.2:c.1397_1399del NP_001268422.1:p.Pro466_Phe467delinsLeu inframe indel NM_001281494.2:c.1397_1399del NP_001268423.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406795.1:c.2399_2401delCTT NP_001393724.1:p.Pro800_Phe801delinsLeu inframe indel NM_001406796.1:c.2303_2305delCTT NP_001393725.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406797.1:c.2006_2008delCTT NP_001393726.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406798.1:c.2303_2305delCTT NP_001393727.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406799.1:c.1778_1780delCTT NP_001393728.1:p.Pro593_Phe594delinsLeu inframe indel NM_001406800.1:c.2303_2305delCTT NP_001393729.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406801.1:c.2006_2008delCTT NP_001393730.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406802.1:c.2399_2401delCTT NP_001393731.1:p.Pro800_Phe801delinsLeu inframe indel NM_001406803.1:c.2303_2305delCTT NP_001393732.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406804.1:c.2225_2227delCTT NP_001393733.1:p.Pro742_Phe743delinsLeu inframe indel NM_001406805.1:c.2006_2008delCTT NP_001393734.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406806.1:c.1778_1780delCTT NP_001393735.1:p.Pro593_Phe594delinsLeu inframe indel NM_001406807.1:c.1778_1780delCTT NP_001393736.1:p.Pro593_Phe594delinsLeu inframe indel NM_001406808.1:c.2303_2305delCTT NP_001393737.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406809.1:c.2303_2305delCTT NP_001393738.1:p.Pro768_Phe769delinsLeu inframe indel NM_001406811.1:c.1397_1399delCTT NP_001393740.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406812.1:c.1397_1399delCTT NP_001393741.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406813.1:c.2309_2311delCTT NP_001393742.1:p.Pro770_Phe771delinsLeu inframe indel NM_001406814.1:c.1397_1399delCTT NP_001393743.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406815.1:c.1397_1399delCTT NP_001393744.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406816.1:c.1397_1399delCTT NP_001393745.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406818.1:c.2006_2008delCTT NP_001393747.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406819.1:c.2006_2008delCTT NP_001393748.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406820.1:c.2006_2008delCTT NP_001393749.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406821.1:c.2006_2008delCTT NP_001393750.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406822.1:c.2006_2008delCTT NP_001393751.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406823.1:c.1397_1399delCTT NP_001393752.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406824.1:c.2006_2008delCTT NP_001393753.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406825.1:c.2006_2008delCTT NP_001393754.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406826.1:c.2135_2137delCTT NP_001393755.1:p.Pro712_Phe713delinsLeu inframe indel NM_001406827.1:c.2006_2008delCTT NP_001393756.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406828.1:c.2006_2008delCTT NP_001393757.1:p.Pro669_Phe670delinsLeu inframe indel NM_001406829.1:c.1397_1399delCTT NP_001393758.1:p.Pro466_Phe467delinsLeu inframe indel NM_001406830.1:c.2006_2008delCTT NP_001393759.1:p.Pro669_Phe670delinsLeu inframe indel NR_176256.1:n.1165_1167delCTT NR_176257.1:n.2392_2394delCTT NR_176258.1:n.2392_2394delCTT NR_176259.1:n.2392_2394delCTT NR_176261.1:n.2392_2394delCTT NC_000002.12:g.47800286_47800288del NC_000002.11:g.48027425_48027427del NG_007111.1:g.22140_22142del LRG_219:g.22140_22142del LRG_219t1:c.2303_2305del LRG_219p1:p.Pro768_Phe769delinsLeu - Protein change
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- Other names
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- Canonical SPDI
- NC_000002.12:47800285:CTT:
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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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 28, 2022 | RCV003030594.3 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Mar 28, 2022)
|
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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003335460.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 variant, c.2303_2305del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the MSH6 protein (p.Pro768_Phe769delinsLeu). (less)
|
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:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 variant, c.2303_2305del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the MSH6 protein (p.Pro768_Phe769delinsLeu).
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 Sep 29, 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.