ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1257dup (p.Glu420Ter)
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.1257dup (p.Glu420Ter)
Variation ID: 2764913 Accession: VCV002764913.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2062007-2062008 (GRCh38) [ NCBI UCSC ] 16: 2112008-2112009 (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 Jun 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.1257dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Glu420Ter nonsense NM_001077183.3:c.1257dup NP_001070651.1:p.Glu420Ter nonsense NM_001114382.3:c.1257dup NP_001107854.1:p.Glu420Ter nonsense NM_001318827.2:c.1146dup NP_001305756.1:p.Glu383Ter nonsense NM_001318829.2:c.1110dup NP_001305758.1:p.Glu371Ter nonsense NM_001318831.2:c.657dup NP_001305760.1:p.Glu220Ter nonsense NM_001318832.2:c.1290dup NP_001305761.1:p.Glu431Ter nonsense NM_001363528.2:c.1257dup NP_001350457.1:p.Glu420Ter nonsense NM_001370404.1:c.1257dup NP_001357333.1:p.Glu420Ter nonsense NM_001370405.1:c.1257dup NP_001357334.1:p.Glu420Ter nonsense NM_001406663.1:c.1257dup NP_001393592.1:p.Glu420Ter nonsense NM_001406664.1:c.1257dup NP_001393593.1:p.Glu420Ter nonsense NM_001406665.1:c.1257dup NP_001393594.1:p.Glu420Ter nonsense NM_001406667.1:c.1347dup NP_001393596.1:p.Glu450Ter nonsense NM_001406668.1:c.1347dup NP_001393597.1:p.Glu450Ter nonsense NM_001406670.1:c.1146dup NP_001393599.1:p.Glu383Ter nonsense NM_001406671.1:c.1245dup NP_001393600.1:p.Glu416Ter nonsense NM_001406673.1:c.1245dup NP_001393602.1:p.Glu416Ter nonsense NM_001406675.1:c.1110dup NP_001393604.1:p.Glu371Ter nonsense NM_001406676.1:c.1110dup NP_001393605.1:p.Glu371Ter nonsense NM_001406677.1:c.1200dup NP_001393606.1:p.Glu401Ter nonsense NM_001406678.1:c.1146dup NP_001393607.1:p.Glu383Ter nonsense NM_001406679.1:c.1110dup NP_001393608.1:p.Glu371Ter nonsense NM_001406680.1:c.657dup NP_001393609.1:p.Glu220Ter nonsense NM_001406681.1:c.795dup NP_001393610.1:p.Glu266Ter nonsense NM_001406682.1:c.657dup NP_001393611.1:p.Glu220Ter nonsense NM_001406683.1:c.657dup NP_001393612.1:p.Glu220Ter nonsense NM_001406684.1:c.657dup NP_001393613.1:p.Glu220Ter nonsense NM_001406685.1:c.657dup NP_001393614.1:p.Glu220Ter nonsense NM_001406686.1:c.657dup NP_001393615.1:p.Glu220Ter nonsense NM_001406687.1:c.657dup NP_001393616.1:p.Glu220Ter nonsense NM_001406688.1:c.657dup NP_001393617.1:p.Glu220Ter nonsense NM_001406689.1:c.-88dup 5 prime UTR NM_001406690.1:c.-88dup 5 prime UTR NM_001406691.1:c.-88dup 5 prime UTR NM_001406692.1:c.-88dup 5 prime UTR NM_001406693.1:c.-88dup 5 prime UTR NM_001406694.1:c.-56dup 5 prime UTR NM_001406695.1:c.-56dup 5 prime UTR NM_001406696.1:c.-88dup 5 prime UTR NM_001406697.1:c.-88dup 5 prime UTR NM_001406698.1:c.-264dup 5 prime UTR NM_021055.3:c.1257dup NP_066399.2:p.Glu420Ter nonsense NR_176225.1:n.1367dup non-coding transcript variant NR_176226.1:n.1367dup non-coding transcript variant NR_176227.1:n.1367dup non-coding transcript variant NR_176228.1:n.1367dup non-coding transcript variant NR_176229.1:n.1367dup non-coding transcript variant NC_000016.10:g.2062008dup NC_000016.9:g.2112009dup NG_005895.1:g.17703dup LRG_487:g.17703dup LRG_487t1:c.1257dup LRG_487p1:p.Glu420Terfs - Protein change
- E220*, E431*, E371*, E383*, E401*, E450*, E266*, E416*, E420*
- Other names
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- Canonical SPDI
- NC_000016.10:2062007:T:TT
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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 |
10626 | 10801 |
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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Jun 4, 2023 | RCV003512592.1 |
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
(Jun 04, 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: SCV004331774.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with TSC2-related conditions (PMID: 29655203). … (more)
For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with TSC2-related conditions (PMID: 29655203). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu420*) 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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Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders. | Lindy AS | Epilepsia | 2018 | PMID: 29655203 |
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.