ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3794dup (p.Leu1266fs)
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_000548.5(TSC2):c.3794dup (p.Leu1266fs)
Variation ID: 2860080 Accession: VCV002860080.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2081776-2081777 (GRCh38) [ NCBI UCSC ] 16: 2131777-2131778 (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 20, 2024 Feb 20, 2024 Apr 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.3794dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Leu1266fs frameshift NM_001077183.3:c.3662dup NP_001070651.1:p.Leu1222fs frameshift NM_001114382.3:c.3794dup NP_001107854.1:p.Leu1266fs frameshift NM_001318827.2:c.3554dup NP_001305756.1:p.Leu1186fs frameshift NM_001318829.2:c.3518dup NP_001305758.1:p.Leu1174fs frameshift NM_001318831.2:c.3062dup NP_001305760.1:p.Leu1022fs frameshift NM_001318832.2:c.3695dup NP_001305761.1:p.Leu1233fs frameshift NM_001363528.2:c.3665dup NP_001350457.1:p.Leu1223fs frameshift NM_001370404.1:c.3662dup NP_001357333.1:p.Leu1222fs frameshift NM_001370405.1:c.3665dup NP_001357334.1:p.Leu1223fs frameshift NM_001406663.1:c.3791dup NP_001393592.1:p.Leu1265fs frameshift NM_001406664.1:c.3791dup NP_001393593.1:p.Leu1265fs frameshift NM_001406665.1:c.3662dup NP_001393594.1:p.Leu1222fs frameshift NM_001406667.1:c.3755dup NP_001393596.1:p.Leu1253fs frameshift NM_001406668.1:c.3752dup NP_001393597.1:p.Leu1252fs frameshift NM_001406670.1:c.3683dup NP_001393599.1:p.Leu1229fs frameshift NM_001406671.1:c.3653dup NP_001393600.1:p.Leu1219fs frameshift NM_001406673.1:c.3650dup NP_001393602.1:p.Leu1218fs frameshift NM_001406675.1:c.3647dup NP_001393604.1:p.Leu1217fs frameshift NM_001406676.1:c.3644dup NP_001393605.1:p.Leu1216fs frameshift NM_001406677.1:c.3605dup NP_001393606.1:p.Leu1203fs frameshift NM_001406678.1:c.3551dup NP_001393607.1:p.Leu1185fs frameshift NM_001406679.1:c.3515dup NP_001393608.1:p.Leu1173fs frameshift NM_001406680.1:c.3194dup NP_001393609.1:p.Leu1066fs frameshift NM_001406681.1:c.3203dup NP_001393610.1:p.Leu1069fs frameshift NM_001406682.1:c.3194dup NP_001393611.1:p.Leu1066fs frameshift NM_001406683.1:c.3194dup NP_001393612.1:p.Leu1066fs frameshift NM_001406684.1:c.3191dup NP_001393613.1:p.Leu1065fs frameshift NM_001406685.1:c.3065dup NP_001393614.1:p.Leu1023fs frameshift NM_001406686.1:c.3065dup NP_001393615.1:p.Leu1023fs frameshift NM_001406687.1:c.3062dup NP_001393616.1:p.Leu1022fs frameshift NM_001406688.1:c.3062dup NP_001393617.1:p.Leu1022fs frameshift NM_001406689.1:c.2450dup NP_001393618.1:p.Leu818fs frameshift NM_001406690.1:c.2321dup NP_001393619.1:p.Leu775fs frameshift NM_001406691.1:c.2318dup NP_001393620.1:p.Leu774fs frameshift NM_001406692.1:c.2321dup NP_001393621.1:p.Leu775fs frameshift NM_001406693.1:c.2321dup NP_001393622.1:p.Leu775fs frameshift NM_001406694.1:c.2321dup NP_001393623.1:p.Leu775fs frameshift NM_001406695.1:c.2318dup NP_001393624.1:p.Leu774fs frameshift NM_001406696.1:c.2318dup NP_001393625.1:p.Leu774fs frameshift NM_001406697.1:c.2318dup NP_001393626.1:p.Leu774fs frameshift NM_001406698.1:c.2060dup NP_001393627.1:p.Leu688fs frameshift NM_021055.3:c.3665dup NP_066399.2:p.Leu1223fs frameshift NR_176225.1:n.3815dup non-coding transcript variant NR_176226.1:n.3994dup non-coding transcript variant NR_176227.1:n.3991dup non-coding transcript variant NR_176228.1:n.3812dup non-coding transcript variant NR_176229.1:n.3772dup non-coding transcript variant NC_000016.10:g.2081778dup NC_000016.9:g.2131779dup NG_005895.1:g.37473dup LRG_487:g.37473dup LRG_487t1:c.3794dup LRG_487p1:p.Leu1266Serfs - Protein change
- L1023fs, L1185fs, L1186fs, L1203fs, L1218fs, L1229fs, L774fs, L1065fs, L1066fs, L1219fs, L1233fs, L1252fs, L1266fs, L818fs, L1069fs, L1174fs, L1216fs, L1217fs, L1223fs, L688fs, L1022fs, L1173fs, L1222fs, L1253fs, L1265fs, L775fs
- Other names
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- Canonical SPDI
- NC_000016.10:2081776:CC:CCC
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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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TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10625 | 10800 |
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
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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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Apr 28, 2023 | RCV003626194.1 |
Submissions - Germline
Classification
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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
(Apr 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004461599.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1266Serfs*56) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). (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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Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. | Au KS | Genetics in medicine : official journal of the American College of Medical Genetics | 2007 | PMID: 17304050 |
Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. | Jones AC | American journal of human genetics | 1999 | PMID: 10205261 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 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.