ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3774del (p.Ser1259fs)
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.3774del (p.Ser1259fs)
Variation ID: 2816462 Accession: VCV002816462.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2081757 (GRCh38) [ NCBI UCSC ] 16: 2131758 (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 20, 2024 Feb 20, 2024 Dec 22, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.3774del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1259fs frameshift NM_001077183.3:c.3642del NP_001070651.1:p.Ser1215fs frameshift NM_001114382.3:c.3774del NP_001107854.1:p.Ser1259fs frameshift NM_001318827.2:c.3534del NP_001305756.1:p.Ser1179fs frameshift NM_001318829.2:c.3498del NP_001305758.1:p.Ser1167fs frameshift NM_001318831.2:c.3042del NP_001305760.1:p.Ser1015fs frameshift NM_001318832.2:c.3675del NP_001305761.1:p.Ser1226fs frameshift NM_001363528.2:c.3645del NP_001350457.1:p.Ser1216fs frameshift NM_001370404.1:c.3642del NP_001357333.1:p.Ser1215fs frameshift NM_001370405.1:c.3645del NP_001357334.1:p.Ser1216fs frameshift NM_001406663.1:c.3771del NP_001393592.1:p.Ser1258fs frameshift NM_001406664.1:c.3771del NP_001393593.1:p.Ser1258fs frameshift NM_001406665.1:c.3642del NP_001393594.1:p.Ser1215fs frameshift NM_001406667.1:c.3735del NP_001393596.1:p.Ser1246fs frameshift NM_001406668.1:c.3732del NP_001393597.1:p.Ser1245fs frameshift NM_001406670.1:c.3663del NP_001393599.1:p.Ser1222fs frameshift NM_001406671.1:c.3633del NP_001393600.1:p.Ser1212fs frameshift NM_001406673.1:c.3630del NP_001393602.1:p.Ser1211fs frameshift NM_001406675.1:c.3627del NP_001393604.1:p.Ser1210fs frameshift NM_001406676.1:c.3624del NP_001393605.1:p.Ser1209fs frameshift NM_001406677.1:c.3585del NP_001393606.1:p.Ser1196fs frameshift NM_001406678.1:c.3531del NP_001393607.1:p.Ser1178fs frameshift NM_001406679.1:c.3495del NP_001393608.1:p.Ser1166fs frameshift NM_001406680.1:c.3174del NP_001393609.1:p.Ser1059fs frameshift NM_001406681.1:c.3183del NP_001393610.1:p.Ser1062fs frameshift NM_001406682.1:c.3174del NP_001393611.1:p.Ser1059fs frameshift NM_001406683.1:c.3174del NP_001393612.1:p.Ser1059fs frameshift NM_001406684.1:c.3171del NP_001393613.1:p.Ser1058fs frameshift NM_001406685.1:c.3045del NP_001393614.1:p.Ser1016fs frameshift NM_001406686.1:c.3045del NP_001393615.1:p.Ser1016fs frameshift NM_001406687.1:c.3042del NP_001393616.1:p.Ser1015fs frameshift NM_001406688.1:c.3042del NP_001393617.1:p.Ser1015fs frameshift NM_001406689.1:c.2430del NP_001393618.1:p.Ser811fs frameshift NM_001406690.1:c.2301del NP_001393619.1:p.Ser768fs frameshift NM_001406691.1:c.2298del NP_001393620.1:p.Ser767fs frameshift NM_001406692.1:c.2301del NP_001393621.1:p.Ser768fs frameshift NM_001406693.1:c.2301del NP_001393622.1:p.Ser768fs frameshift NM_001406694.1:c.2301del NP_001393623.1:p.Ser768fs frameshift NM_001406695.1:c.2298del NP_001393624.1:p.Ser767fs frameshift NM_001406696.1:c.2298del NP_001393625.1:p.Ser767fs frameshift NM_001406697.1:c.2298del NP_001393626.1:p.Ser767fs frameshift NM_001406698.1:c.2040del NP_001393627.1:p.Ser681fs frameshift NM_021055.3:c.3645del NP_066399.2:p.Ser1216fs frameshift NR_176225.1:n.3795del non-coding transcript variant NR_176226.1:n.3974del non-coding transcript variant NR_176227.1:n.3971del non-coding transcript variant NR_176228.1:n.3792del non-coding transcript variant NR_176229.1:n.3752del non-coding transcript variant NC_000016.10:g.2081758del NC_000016.9:g.2131759del NG_005895.1:g.37453del LRG_487:g.37453del LRG_487t1:c.3774del LRG_487p1:p.Ser1259Alafs - Protein change
- S1058fs, S1167fs, S1179fs, S1196fs, S1216fs, S1258fs, S1212fs, S1246fs, S681fs, S811fs, S1015fs, S1059fs, S1062fs, S1178fs, S1209fs, S1222fs, S1226fs, S767fs, S1016fs, S1166fs, S1210fs, S1211fs, S1215fs, S1245fs, S1259fs, S768fs
- Other names
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- Canonical SPDI
- NC_000016.10:2081756:CC:C
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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 22, 2022 | RCV003627904.1 |
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
(Dec 22, 2022)
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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: SCV004409407.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 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.Ser1259Alafs*66) 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 Feb 29, 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.