ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1399dup (p.Asp467fs)
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.1399dup (p.Asp467fs)
Variation ID: 2757653 Accession: VCV002757653.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2063007-2063008 (GRCh38) [ NCBI UCSC ] 16: 2113008-2113009 (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 14, 2024 Feb 14, 2024 Sep 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.1399dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Asp467fs frameshift NM_001077183.3:c.1399dup NP_001070651.1:p.Asp467fs frameshift NM_001114382.3:c.1399dup NP_001107854.1:p.Asp467fs frameshift NM_001318827.2:c.1288dup NP_001305756.1:p.Asp430fs frameshift NM_001318829.2:c.1252dup NP_001305758.1:p.Asp418fs frameshift NM_001318831.2:c.799dup NP_001305760.1:p.Asp267fs frameshift NM_001318832.2:c.1432dup NP_001305761.1:p.Asp478fs frameshift NM_001363528.2:c.1399dup NP_001350457.1:p.Asp467fs frameshift NM_001370404.1:c.1399dup NP_001357333.1:p.Asp467fs frameshift NM_001370405.1:c.1399dup NP_001357334.1:p.Asp467fs frameshift NM_001406663.1:c.1399dup NP_001393592.1:p.Asp467fs frameshift NM_001406664.1:c.1399dup NP_001393593.1:p.Asp467fs frameshift NM_001406665.1:c.1399dup NP_001393594.1:p.Asp467fs frameshift NM_001406667.1:c.1489dup NP_001393596.1:p.Asp497fs frameshift NM_001406668.1:c.1489dup NP_001393597.1:p.Asp497fs frameshift NM_001406670.1:c.1288dup NP_001393599.1:p.Asp430fs frameshift NM_001406671.1:c.1387dup NP_001393600.1:p.Asp463fs frameshift NM_001406673.1:c.1387dup NP_001393602.1:p.Asp463fs frameshift NM_001406675.1:c.1252dup NP_001393604.1:p.Asp418fs frameshift NM_001406676.1:c.1252dup NP_001393605.1:p.Asp418fs frameshift NM_001406677.1:c.1342dup NP_001393606.1:p.Asp448fs frameshift NM_001406678.1:c.1288dup NP_001393607.1:p.Asp430fs frameshift NM_001406679.1:c.1252dup NP_001393608.1:p.Asp418fs frameshift NM_001406680.1:c.799dup NP_001393609.1:p.Asp267fs frameshift NM_001406681.1:c.937dup NP_001393610.1:p.Asp313fs frameshift NM_001406682.1:c.799dup NP_001393611.1:p.Asp267fs frameshift NM_001406683.1:c.799dup NP_001393612.1:p.Asp267fs frameshift NM_001406684.1:c.799dup NP_001393613.1:p.Asp267fs frameshift NM_001406685.1:c.799dup NP_001393614.1:p.Asp267fs frameshift NM_001406686.1:c.799dup NP_001393615.1:p.Asp267fs frameshift NM_001406687.1:c.799dup NP_001393616.1:p.Asp267fs frameshift NM_001406688.1:c.799dup NP_001393617.1:p.Asp267fs frameshift NM_001406689.1:c.55dup NP_001393618.1:p.Asp19fs frameshift NM_001406690.1:c.55dup NP_001393619.1:p.Asp19fs frameshift NM_001406691.1:c.55dup NP_001393620.1:p.Asp19fs frameshift NM_001406692.1:c.55dup NP_001393621.1:p.Asp19fs frameshift NM_001406693.1:c.55dup NP_001393622.1:p.Asp19fs frameshift NM_001406694.1:c.55dup NP_001393623.1:p.Asp19fs frameshift NM_001406695.1:c.55dup NP_001393624.1:p.Asp19fs frameshift NM_001406696.1:c.55dup NP_001393625.1:p.Asp19fs frameshift NM_001406697.1:c.55dup NP_001393626.1:p.Asp19fs frameshift NM_001406698.1:c.-160+409dup intron variant NM_021055.3:c.1399dup NP_066399.2:p.Asp467fs frameshift NR_176225.1:n.1509dup non-coding transcript variant NR_176226.1:n.1509dup non-coding transcript variant NR_176227.1:n.1509dup non-coding transcript variant NR_176228.1:n.1509dup non-coding transcript variant NR_176229.1:n.1509dup non-coding transcript variant NC_000016.10:g.2063009dup NC_000016.9:g.2113010dup NG_005895.1:g.18704dup LRG_487:g.18704dup LRG_487t1:c.1399dup LRG_487p1:p.Asp467Glyfs - Protein change
- D19fs, D448fs, D313fs, D430fs, D467fs, D418fs, D463fs, D497fs, D267fs, D478fs
- Other names
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- Canonical SPDI
- NC_000016.10:2063007:GG:GGG
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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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Sep 3, 2023 | RCV003511899.1 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
(Sep 03, 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: SCV004320287.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp467Glyfs*15) in the TSC2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Asp467Glyfs*15) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (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 20, 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.