ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4198_4207del (p.Asp1400fs)
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.4198_4207del (p.Asp1400fs)
Variation ID: 2765855 Accession: VCV002765855.1
- Type and length
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Deletion, 10 bp
- Location
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Cytogenetic: 16p13.3 16: 2084417-2084426 (GRCh38) [ NCBI UCSC ] 16: 2134418-2134427 (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 Oct 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4198_4207del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Asp1400fs frameshift NM_001077183.3:c.3997_4006del NP_001070651.1:p.Asp1333fs frameshift NM_001114382.3:c.4129_4138del NP_001107854.1:p.Asp1377fs frameshift NM_001318827.2:c.3889_3898del NP_001305756.1:p.Asp1297fs frameshift NM_001318829.2:c.3853_3862del NP_001305758.1:p.Asp1285fs frameshift NM_001318831.2:c.3466_3475del NP_001305760.1:p.Asp1156fs frameshift NM_001318832.2:c.4030_4039del NP_001305761.1:p.Asp1344fs frameshift NM_001363528.2:c.4000_4009del NP_001350457.1:p.Asp1334fs frameshift NM_001370404.1:c.4066_4075del NP_001357333.1:p.Asp1356fs frameshift NM_001370405.1:c.4069_4078del NP_001357334.1:p.Asp1357fs frameshift NM_001406663.1:c.4195_4204del NP_001393592.1:p.Asp1399fs frameshift NM_001406664.1:c.4126_4135del NP_001393593.1:p.Asp1376fs frameshift NM_001406665.1:c.4120_4129del NP_001393594.1:p.Asp1374fs frameshift NM_001406667.1:c.4090_4099del NP_001393596.1:p.Asp1364fs frameshift NM_001406668.1:c.4087_4096del NP_001393597.1:p.Asp1363fs frameshift NM_001406670.1:c.4018_4027del NP_001393599.1:p.Asp1340fs frameshift NM_001406671.1:c.3988_3997del NP_001393600.1:p.Asp1330fs frameshift NM_001406673.1:c.3985_3994del NP_001393602.1:p.Asp1329fs frameshift NM_001406675.1:c.3982_3991del NP_001393604.1:p.Asp1328fs frameshift NM_001406676.1:c.3979_3988del NP_001393605.1:p.Asp1327fs frameshift NM_001406677.1:c.3940_3949del NP_001393606.1:p.Asp1314fs frameshift NM_001406678.1:c.3886_3895del NP_001393607.1:p.Asp1296fs frameshift NM_001406679.1:c.3850_3859del NP_001393608.1:p.Asp1284fs frameshift NM_001406680.1:c.3598_3607del NP_001393609.1:p.Asp1200fs frameshift NM_001406681.1:c.3538_3547del NP_001393610.1:p.Asp1180fs frameshift NM_001406682.1:c.3529_3538del NP_001393611.1:p.Asp1177fs frameshift NM_001406683.1:c.3529_3538del NP_001393612.1:p.Asp1177fs frameshift NM_001406684.1:c.3526_3535del NP_001393613.1:p.Asp1176fs frameshift NM_001406685.1:c.3400_3409del NP_001393614.1:p.Asp1134fs frameshift NM_001406686.1:c.3400_3409del NP_001393615.1:p.Asp1134fs frameshift NM_001406687.1:c.3397_3406del NP_001393616.1:p.Asp1133fs frameshift NM_001406688.1:c.3397_3406del NP_001393617.1:p.Asp1133fs frameshift NM_001406689.1:c.2785_2794del NP_001393618.1:p.Asp929fs frameshift NM_001406690.1:c.2725_2734del NP_001393619.1:p.Asp909fs frameshift NM_001406691.1:c.2722_2731del NP_001393620.1:p.Asp908fs frameshift NM_001406692.1:c.2656_2665del NP_001393621.1:p.Asp886fs frameshift NM_001406693.1:c.2656_2665del NP_001393622.1:p.Asp886fs frameshift NM_001406694.1:c.2656_2665del NP_001393623.1:p.Asp886fs frameshift NM_001406695.1:c.2653_2662del NP_001393624.1:p.Asp885fs frameshift NM_001406696.1:c.2653_2662del NP_001393625.1:p.Asp885fs frameshift NM_001406697.1:c.2653_2662del NP_001393626.1:p.Asp885fs frameshift NM_001406698.1:c.2395_2404del NP_001393627.1:p.Asp799fs frameshift NM_021055.3:c.4069_4078del NP_066399.2:p.Asp1357fs frameshift NR_176225.1:n.4150_4159del non-coding transcript variant NR_176226.1:n.4398_4407del non-coding transcript variant NR_176227.1:n.4326_4335del non-coding transcript variant NR_176228.1:n.4147_4156del non-coding transcript variant NR_176229.1:n.4107_4116del non-coding transcript variant NC_000016.10:g.2084420_2084429del NC_000016.9:g.2134421_2134430del NG_005895.1:g.40115_40124del LRG_487:g.40115_40124del LRG_487t1:c.4198_4207del LRG_487p1:p.Asp1400Thrfs - Protein change
- D1133fs, D1180fs, D1329fs, D1333fs, D1334fs, D1364fs, D1376fs, D885fs, D886fs, D1156fs, D1176fs, D1177fs, D1284fs, D1285fs, D1296fs, D1297fs, D1314fs, D1356fs, D1357fs, D1374fs, D1399fs, D1400fs, D799fs, D908fs, D929fs, D1134fs, D1327fs, D1328fs, D1330fs, D1340fs, D909fs, D1200fs, D1344fs, D1363fs, D1377fs
- Other names
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- Canonical SPDI
- NC_000016.10:2084416:GGGGACCCTGGGG: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
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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Oct 5, 2023 | RCV003512618.1 |
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
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
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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
(Oct 05, 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: SCV004330323.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp1400Thrfs*8) 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.Asp1400Thrfs*8) 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. 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.