ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4557del (p.Leu1520fs)
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.4557del (p.Leu1520fs)
Variation ID: 2759833 Accession: VCV002759833.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2085014 (GRCh38) [ NCBI UCSC ] 16: 2135015 (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 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4557del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Leu1520fs frameshift NM_001077183.3:c.4356del NP_001070651.1:p.Leu1453fs frameshift NM_001114382.3:c.4488del NP_001107854.1:p.Leu1497fs frameshift NM_001318827.2:c.4248del NP_001305756.1:p.Leu1417fs frameshift NM_001318829.2:c.4212del NP_001305758.1:p.Leu1405fs frameshift NM_001318831.2:c.3825del NP_001305760.1:p.Leu1276fs frameshift NM_001318832.2:c.4389del NP_001305761.1:p.Leu1464fs frameshift NM_001363528.2:c.4359del NP_001350457.1:p.Leu1454fs frameshift NM_001370404.1:c.4425del NP_001357333.1:p.Leu1476fs frameshift NM_001370405.1:c.4428del NP_001357334.1:p.Leu1477fs frameshift NM_001406663.1:c.4554del NP_001393592.1:p.Leu1519fs frameshift NM_001406664.1:c.4485del NP_001393593.1:p.Leu1496fs frameshift NM_001406665.1:c.4479del NP_001393594.1:p.Leu1494fs frameshift NM_001406667.1:c.4449del NP_001393596.1:p.Leu1484fs frameshift NM_001406668.1:c.4446del NP_001393597.1:p.Leu1483fs frameshift NM_001406670.1:c.4377del NP_001393599.1:p.Leu1460fs frameshift NM_001406671.1:c.4347del NP_001393600.1:p.Leu1450fs frameshift NM_001406673.1:c.4344del NP_001393602.1:p.Leu1449fs frameshift NM_001406675.1:c.4341del NP_001393604.1:p.Leu1448fs frameshift NM_001406676.1:c.4338del NP_001393605.1:p.Leu1447fs frameshift NM_001406677.1:c.4299del NP_001393606.1:p.Leu1434fs frameshift NM_001406678.1:c.4245del NP_001393607.1:p.Leu1416fs frameshift NM_001406679.1:c.4209del NP_001393608.1:p.Leu1404fs frameshift NM_001406680.1:c.3957del NP_001393609.1:p.Leu1320fs frameshift NM_001406681.1:c.3897del NP_001393610.1:p.Leu1300fs frameshift NM_001406682.1:c.3888del NP_001393611.1:p.Leu1297fs frameshift NM_001406683.1:c.3888del NP_001393612.1:p.Leu1297fs frameshift NM_001406684.1:c.3885del NP_001393613.1:p.Leu1296fs frameshift NM_001406685.1:c.3759del NP_001393614.1:p.Leu1254fs frameshift NM_001406686.1:c.3759del NP_001393615.1:p.Leu1254fs frameshift NM_001406687.1:c.3756del NP_001393616.1:p.Leu1253fs frameshift NM_001406688.1:c.3756del NP_001393617.1:p.Leu1253fs frameshift NM_001406689.1:c.3144del NP_001393618.1:p.Leu1049fs frameshift NM_001406690.1:c.3084del NP_001393619.1:p.Leu1029fs frameshift NM_001406691.1:c.3081del NP_001393620.1:p.Leu1028fs frameshift NM_001406692.1:c.3015del NP_001393621.1:p.Leu1006fs frameshift NM_001406693.1:c.3015del NP_001393622.1:p.Leu1006fs frameshift NM_001406694.1:c.3015del NP_001393623.1:p.Leu1006fs frameshift NM_001406695.1:c.3012del NP_001393624.1:p.Leu1005fs frameshift NM_001406696.1:c.3012del NP_001393625.1:p.Leu1005fs frameshift NM_001406697.1:c.3012del NP_001393626.1:p.Leu1005fs frameshift NM_001406698.1:c.2754del NP_001393627.1:p.Leu919fs frameshift NM_021055.3:c.4428del NP_066399.2:p.Leu1477fs frameshift NR_176225.1:n.4509del non-coding transcript variant NR_176226.1:n.4757del non-coding transcript variant NR_176227.1:n.4685del non-coding transcript variant NR_176228.1:n.4506del non-coding transcript variant NR_176229.1:n.4466del non-coding transcript variant NC_000016.10:g.2085014del NC_000016.9:g.2135015del NG_005895.1:g.40709del LRG_487:g.40709del LRG_487t1:c.4557del LRG_487p1:p.Leu1520Cysfs - Protein change
- L1005fs, L1028fs, L1296fs, L1253fs, L1300fs, L1405fs, L1416fs, L1453fs, L1464fs, L1483fs, L1496fs, L1320fs, L1434fs, L1447fs, L1477fs, L1497fs, L1519fs, L1520fs, L1029fs, L1254fs, L1276fs, L1297fs, L1417fs, L1450fs, L1476fs, L1484fs, L1006fs, L1049fs, L1404fs, L1448fs, L1449fs, L1454fs, L1460fs, L1494fs, L919fs
- Other names
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- Canonical SPDI
- NC_000016.10:2085013:G:
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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 |
10735 | 10932 |
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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Sep 10, 2023 | RCV003511966.2 |
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
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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 10, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004322368.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not … (more)
This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This sequence change creates a premature translational stop signal (p.Leu1520Cysfs*56) 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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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 Sep 30, 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.