ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4593_4594delinsTT (p.Gln1532Ter)
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.4593_4594delinsTT (p.Gln1532Ter)
Variation ID: 2706790 Accession: VCV002706790.1
- Type and length
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Indel, 2 bp
- Location
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Cytogenetic: 16p13.3 16: 2085253-2085254 (GRCh38) [ NCBI UCSC ] 16: 2135254-2135255 (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 Dec 31, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4593_4594delinsTT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Gln1532Ter nonsense NM_001077183.3:c.4392_4393delinsTT NP_001070651.1:p.Gln1465Ter nonsense NM_001114382.3:c.4524_4525delinsTT NP_001107854.1:p.Gln1509Ter nonsense NM_001318827.2:c.4284_4285delinsTT NP_001305756.1:p.Gln1429Ter nonsense NM_001318829.2:c.4248_4249delinsTT NP_001305758.1:p.Gln1417Ter nonsense NM_001318831.2:c.3861_3862delinsTT NP_001305760.1:p.Gln1288Ter nonsense NM_001318832.2:c.4425_4426delinsTT NP_001305761.1:p.Gln1476Ter nonsense NM_001363528.2:c.4395_4396delinsTT NP_001350457.1:p.Gln1466Ter nonsense NM_001370404.1:c.4461_4462delinsTT NP_001357333.1:p.Gln1488Ter nonsense NM_001370405.1:c.4464_4465delinsTT NP_001357334.1:p.Gln1489Ter nonsense NM_001406663.1:c.4590_4591delinsTT NP_001393592.1:p.Gln1531Ter nonsense NM_001406664.1:c.4521_4522delinsTT NP_001393593.1:p.Gln1508Ter nonsense NM_001406665.1:c.4515_4516delinsTT NP_001393594.1:p.Gln1506Ter nonsense NM_001406667.1:c.4485_4486delinsTT NP_001393596.1:p.Gln1496Ter nonsense NM_001406668.1:c.4482_4483delinsTT NP_001393597.1:p.Gln1495Ter nonsense NM_001406670.1:c.4413_4414delinsTT NP_001393599.1:p.Gln1472Ter nonsense NM_001406671.1:c.4383_4384delinsTT NP_001393600.1:p.Gln1462Ter nonsense NM_001406673.1:c.4380_4381delinsTT NP_001393602.1:p.Gln1461Ter nonsense NM_001406675.1:c.4377_4378delinsTT NP_001393604.1:p.Gln1460Ter nonsense NM_001406676.1:c.4374_4375delinsTT NP_001393605.1:p.Gln1459Ter nonsense NM_001406677.1:c.4335_4336delinsTT NP_001393606.1:p.Gln1446Ter nonsense NM_001406678.1:c.4281_4282delinsTT NP_001393607.1:p.Gln1428Ter nonsense NM_001406679.1:c.4245_4246delinsTT NP_001393608.1:p.Gln1416Ter nonsense NM_001406680.1:c.3993_3994delinsTT NP_001393609.1:p.Gln1332Ter nonsense NM_001406681.1:c.3933_3934delinsTT NP_001393610.1:p.Gln1312Ter nonsense NM_001406682.1:c.3924_3925delinsTT NP_001393611.1:p.Gln1309Ter nonsense NM_001406683.1:c.3924_3925delinsTT NP_001393612.1:p.Gln1309Ter nonsense NM_001406684.1:c.3921_3922delinsTT NP_001393613.1:p.Gln1308Ter nonsense NM_001406685.1:c.3795_3796delinsTT NP_001393614.1:p.Gln1266Ter nonsense NM_001406686.1:c.3795_3796delinsTT NP_001393615.1:p.Gln1266Ter nonsense NM_001406687.1:c.3792_3793delinsTT NP_001393616.1:p.Gln1265Ter nonsense NM_001406688.1:c.3792_3793delinsTT NP_001393617.1:p.Gln1265Ter nonsense NM_001406689.1:c.3180_3181delinsTT NP_001393618.1:p.Gln1061Ter nonsense NM_001406690.1:c.3120_3121delinsTT NP_001393619.1:p.Gln1041Ter nonsense NM_001406691.1:c.3117_3118delinsTT NP_001393620.1:p.Gln1040Ter nonsense NM_001406692.1:c.3051_3052delinsTT NP_001393621.1:p.Gln1018Ter nonsense NM_001406693.1:c.3051_3052delinsTT NP_001393622.1:p.Gln1018Ter nonsense NM_001406694.1:c.3051_3052delinsTT NP_001393623.1:p.Gln1018Ter nonsense NM_001406695.1:c.3048_3049delinsTT NP_001393624.1:p.Gln1017Ter nonsense NM_001406696.1:c.3048_3049delinsTT NP_001393625.1:p.Gln1017Ter nonsense NM_001406697.1:c.3048_3049delinsTT NP_001393626.1:p.Gln1017Ter nonsense NM_001406698.1:c.2790_2791delinsTT NP_001393627.1:p.Gln931Ter nonsense NM_021055.3:c.4464_4465delinsTT NP_066399.2:p.Gln1489Ter nonsense NR_176225.1:n.4545_4546delinsTT non-coding transcript variant NR_176226.1:n.4793_4794delinsTT non-coding transcript variant NR_176227.1:n.4721_4722delinsTT non-coding transcript variant NR_176228.1:n.4542_4543delinsTT non-coding transcript variant NR_176229.1:n.4502_4503delinsTT non-coding transcript variant NC_000016.10:g.2085253_2085254delinsTT NC_000016.9:g.2135254_2135255delinsTT NG_005895.1:g.40948_40949delinsTT LRG_487:g.40948_40949delinsTT LRG_487t1:c.4593_4594delGCinsTT LRG_487p1:p.Gln1532Ter - Protein change
- Q1308*, Q1309*, Q1312*, Q1332*, Q1459*, Q1460*, Q1476*, Q1488*, Q1495*, Q1061*, Q1265*, Q1266*, Q1428*, Q1465*, Q1466*, Q1496*, Q1506*, Q1509*, Q931*, Q1018*, Q1040*, Q1288*, Q1416*, Q1429*, Q1446*, Q1461*, Q1462*, Q1472*, Q1508*, Q1532*, Q1017*, Q1041*, Q1417*, Q1489*, Q1531*
- Other names
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- Canonical SPDI
- NC_000016.10:2085252:GC: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 |
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
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
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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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Dec 31, 2023 | RCV003512955.1 |
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
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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
(Dec 31, 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: SCV004260737.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1532*) 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.Gln1532*) 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). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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.