ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.2690del (p.Phe897fs)
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.2690del (p.Phe897fs)
Variation ID: 2736291 Accession: VCV002736291.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2076117 (GRCh38) [ NCBI UCSC ] 16: 2126118 (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 Nov 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.2690del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Phe897fs frameshift NM_001077183.3:c.2690del NP_001070651.1:p.Phe897fs frameshift NM_001114382.3:c.2690del NP_001107854.1:p.Phe897fs frameshift NM_001318827.2:c.2579del NP_001305756.1:p.Phe860fs frameshift NM_001318829.2:c.2543del NP_001305758.1:p.Phe848fs frameshift NM_001318831.2:c.2090del NP_001305760.1:p.Phe697fs frameshift NM_001318832.2:c.2723del NP_001305761.1:p.Phe908fs frameshift NM_001363528.2:c.2690del NP_001350457.1:p.Phe897fs frameshift NM_001370404.1:c.2690del NP_001357333.1:p.Phe897fs frameshift NM_001370405.1:c.2690del NP_001357334.1:p.Phe897fs frameshift NM_001406663.1:c.2690del NP_001393592.1:p.Phe897fs frameshift NM_001406664.1:c.2690del NP_001393593.1:p.Phe897fs frameshift NM_001406665.1:c.2690del NP_001393594.1:p.Phe897fs frameshift NM_001406667.1:c.2780del NP_001393596.1:p.Phe927fs frameshift NM_001406668.1:c.2780del NP_001393597.1:p.Phe927fs frameshift NM_001406670.1:c.2579del NP_001393599.1:p.Phe860fs frameshift NM_001406671.1:c.2678del NP_001393600.1:p.Phe893fs frameshift NM_001406673.1:c.2678del NP_001393602.1:p.Phe893fs frameshift NM_001406675.1:c.2543del NP_001393604.1:p.Phe848fs frameshift NM_001406676.1:c.2543del NP_001393605.1:p.Phe848fs frameshift NM_001406677.1:c.2633del NP_001393606.1:p.Phe878fs frameshift NM_001406678.1:c.2579del NP_001393607.1:p.Phe860fs frameshift NM_001406679.1:c.2543del NP_001393608.1:p.Phe848fs frameshift NM_001406680.1:c.2090del NP_001393609.1:p.Phe697fs frameshift NM_001406681.1:c.2228del NP_001393610.1:p.Phe743fs frameshift NM_001406682.1:c.2090del NP_001393611.1:p.Phe697fs frameshift NM_001406683.1:c.2090del NP_001393612.1:p.Phe697fs frameshift NM_001406684.1:c.2090del NP_001393613.1:p.Phe697fs frameshift NM_001406685.1:c.2090del NP_001393614.1:p.Phe697fs frameshift NM_001406686.1:c.2090del NP_001393615.1:p.Phe697fs frameshift NM_001406687.1:c.2090del NP_001393616.1:p.Phe697fs frameshift NM_001406688.1:c.2090del NP_001393617.1:p.Phe697fs frameshift NM_001406689.1:c.1346del NP_001393618.1:p.Phe449fs frameshift NM_001406690.1:c.1346del NP_001393619.1:p.Phe449fs frameshift NM_001406691.1:c.1346del NP_001393620.1:p.Phe449fs frameshift NM_001406692.1:c.1346del NP_001393621.1:p.Phe449fs frameshift NM_001406693.1:c.1346del NP_001393622.1:p.Phe449fs frameshift NM_001406694.1:c.1346del NP_001393623.1:p.Phe449fs frameshift NM_001406695.1:c.1346del NP_001393624.1:p.Phe449fs frameshift NM_001406696.1:c.1346del NP_001393625.1:p.Phe449fs frameshift NM_001406697.1:c.1346del NP_001393626.1:p.Phe449fs frameshift NM_001406698.1:c.1088del NP_001393627.1:p.Phe363fs frameshift NM_021055.3:c.2690del NP_066399.2:p.Phe897fs frameshift NR_176225.1:n.2840del non-coding transcript variant NR_176226.1:n.3019del non-coding transcript variant NR_176227.1:n.3019del non-coding transcript variant NR_176228.1:n.2840del non-coding transcript variant NR_176229.1:n.2800del non-coding transcript variant NC_000016.10:g.2076118del NC_000016.9:g.2126119del NG_005895.1:g.31813del LRG_487:g.31813del LRG_487t1:c.2690del LRG_487p1:p.Phe897Serfs - Protein change
- F697fs, F743fs, F363fs, F449fs, F860fs, F893fs, F897fs, F927fs, F848fs, F878fs, F908fs
- Other names
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- Canonical SPDI
- NC_000016.10:2076116:TT: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
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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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Nov 11, 2023 | RCV003513635.1 |
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
(Nov 11, 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: SCV004296659.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Phe897Serfs*51) 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.Phe897Serfs*51) 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 premature translational stop signal has been observed in individual(s) with tuberous sclerosis complex (PMID: 24840834). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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A novel TSC2 mutation in a Chinese family with tuberous sclerosis complex. | Yu Z | Journal of genetics | 2014 | PMID: 24840834 |
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.