Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32555378, 29476190)
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4537G>T (p.Glu1513Ter)
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.
Pathogenic
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_000548.5(TSC2):c.4537G>T (p.Glu1513Ter)
Variation ID: 2428816 Accession: VCV002428816.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2084994 (GRCh38) [ NCBI UCSC ] 16: 2134995 (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 13, 2023 Feb 13, 2023 Aug 3, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.4537G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Glu1513Ter nonsense NM_001077183.3:c.4336G>T NP_001070651.1:p.Glu1446Ter nonsense NM_001114382.3:c.4468G>T NP_001107854.1:p.Glu1490Ter nonsense NM_001318827.2:c.4228G>T NP_001305756.1:p.Glu1410Ter nonsense NM_001318829.2:c.4192G>T NP_001305758.1:p.Glu1398Ter nonsense NM_001318831.2:c.3805G>T NP_001305760.1:p.Glu1269Ter nonsense NM_001318832.2:c.4369G>T NP_001305761.1:p.Glu1457Ter nonsense NM_001363528.2:c.4339G>T NP_001350457.1:p.Glu1447Ter nonsense NM_001370404.1:c.4405G>T NP_001357333.1:p.Glu1469Ter nonsense NM_001370405.1:c.4408G>T NP_001357334.1:p.Glu1470Ter nonsense NM_001406663.1:c.4534G>T NP_001393592.1:p.Glu1512Ter nonsense NM_001406664.1:c.4465G>T NP_001393593.1:p.Glu1489Ter nonsense NM_001406665.1:c.4459G>T NP_001393594.1:p.Glu1487Ter nonsense NM_001406667.1:c.4429G>T NP_001393596.1:p.Glu1477Ter nonsense NM_001406668.1:c.4426G>T NP_001393597.1:p.Glu1476Ter nonsense NM_001406670.1:c.4357G>T NP_001393599.1:p.Glu1453Ter nonsense NM_001406671.1:c.4327G>T NP_001393600.1:p.Glu1443Ter nonsense NM_001406673.1:c.4324G>T NP_001393602.1:p.Glu1442Ter nonsense NM_001406675.1:c.4321G>T NP_001393604.1:p.Glu1441Ter nonsense NM_001406676.1:c.4318G>T NP_001393605.1:p.Glu1440Ter nonsense NM_001406677.1:c.4279G>T NP_001393606.1:p.Glu1427Ter nonsense NM_001406678.1:c.4225G>T NP_001393607.1:p.Glu1409Ter nonsense NM_001406679.1:c.4189G>T NP_001393608.1:p.Glu1397Ter nonsense NM_001406680.1:c.3937G>T NP_001393609.1:p.Glu1313Ter nonsense NM_001406681.1:c.3877G>T NP_001393610.1:p.Glu1293Ter nonsense NM_001406682.1:c.3868G>T NP_001393611.1:p.Glu1290Ter nonsense NM_001406683.1:c.3868G>T NP_001393612.1:p.Glu1290Ter nonsense NM_001406684.1:c.3865G>T NP_001393613.1:p.Glu1289Ter nonsense NM_001406685.1:c.3739G>T NP_001393614.1:p.Glu1247Ter nonsense NM_001406686.1:c.3739G>T NP_001393615.1:p.Glu1247Ter nonsense NM_001406687.1:c.3736G>T NP_001393616.1:p.Glu1246Ter nonsense NM_001406688.1:c.3736G>T NP_001393617.1:p.Glu1246Ter nonsense NM_001406689.1:c.3124G>T NP_001393618.1:p.Glu1042Ter nonsense NM_001406690.1:c.3064G>T NP_001393619.1:p.Glu1022Ter nonsense NM_001406691.1:c.3061G>T NP_001393620.1:p.Glu1021Ter nonsense NM_001406692.1:c.2995G>T NP_001393621.1:p.Glu999Ter nonsense NM_001406693.1:c.2995G>T NP_001393622.1:p.Glu999Ter nonsense NM_001406694.1:c.2995G>T NP_001393623.1:p.Glu999Ter nonsense NM_001406695.1:c.2992G>T NP_001393624.1:p.Glu998Ter nonsense NM_001406696.1:c.2992G>T NP_001393625.1:p.Glu998Ter nonsense NM_001406697.1:c.2992G>T NP_001393626.1:p.Glu998Ter nonsense NM_001406698.1:c.2734G>T NP_001393627.1:p.Glu912Ter nonsense NM_021055.3:c.4408G>T NP_066399.2:p.Glu1470Ter nonsense NR_176225.1:n.4489G>T NR_176226.1:n.4737G>T NR_176227.1:n.4665G>T NR_176228.1:n.4486G>T NR_176229.1:n.4446G>T NC_000016.10:g.2084994G>T NC_000016.9:g.2134995G>T NG_005895.1:g.40689G>T LRG_487:g.40689G>T LRG_487t1:c.4537G>T LRG_487p1:p.Glu1513Ter - Protein change
- E1021*, E1022*, E1042*, E1246*, E1247*, E1269*, E1289*, E1290*, E1293*, E1313*, E1397*, E1398*, E1409*, E1410*, E1427*, E1440*, E1441*, E1442*, E1443*, E1446*, E1447*, E1453*, E1457*, E1469*, E1470*, E1476*, E1477*, E1487*, E1489*, E1490*, E1512*, E1513*, E912*, E998*, E999*
- Other names
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- Canonical SPDI
- NC_000016.10:2084993:G:T
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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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| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10754 | 10953 | |
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
|
Aug 3, 2022 | RCV003120417.2 |
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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Pathogenic
(Aug 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003798553.1
First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32555378, 29476190) (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:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32555378, 29476190)
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 Feb 18, 2023
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.