ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3455del (p.Ser1152fs)
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.3455del (p.Ser1152fs)
Variation ID: 2120984 Accession: VCV002120984.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2080222 (GRCh38) [ NCBI UCSC ] 16: 2130223 (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 8, 2023 Feb 20, 2024 Apr 3, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.3455del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1152fs frameshift NM_001077183.3:c.3323del NP_001070651.1:p.Ser1108fs frameshift NM_001114382.3:c.3455del NP_001107854.1:p.Ser1152fs frameshift NM_001318827.2:c.3215del NP_001305756.1:p.Ser1072fs frameshift NM_001318829.2:c.3179del NP_001305758.1:p.Ser1060fs frameshift NM_001318831.2:c.2723del NP_001305760.1:p.Ser908fs frameshift NM_001318832.2:c.3356del NP_001305761.1:p.Ser1119fs frameshift NM_001363528.2:c.3326del NP_001350457.1:p.Ser1109fs frameshift NM_001370404.1:c.3323del NP_001357333.1:p.Ser1108fs frameshift NM_001370405.1:c.3326del NP_001357334.1:p.Ser1109fs frameshift NM_001406663.1:c.3452delG NP_001393592.1:p.Ser1151Metfs frameshift NM_001406664.1:c.3452delG NP_001393593.1:p.Ser1151Metfs frameshift NM_001406665.1:c.3323delG NP_001393594.1:p.Ser1108Metfs frameshift NM_001406667.1:c.3416delG NP_001393596.1:p.Ser1139Metfs frameshift NM_001406668.1:c.3413delG NP_001393597.1:p.Ser1138Metfs frameshift NM_001406670.1:c.3344delG NP_001393599.1:p.Ser1115Metfs frameshift NM_001406671.1:c.3314delG NP_001393600.1:p.Ser1105Metfs frameshift NM_001406673.1:c.3311delG NP_001393602.1:p.Ser1104Metfs frameshift NM_001406675.1:c.3308delG NP_001393604.1:p.Ser1103Metfs frameshift NM_001406676.1:c.3305delG NP_001393605.1:p.Ser1102Metfs frameshift NM_001406677.1:c.3266delG NP_001393606.1:p.Ser1089Metfs frameshift NM_001406678.1:c.3212delG NP_001393607.1:p.Ser1071Metfs frameshift NM_001406679.1:c.3176delG NP_001393608.1:p.Ser1059Metfs frameshift NM_001406680.1:c.2855delG NP_001393609.1:p.Ser952Metfs frameshift NM_001406681.1:c.2864delG NP_001393610.1:p.Ser955Metfs frameshift NM_001406682.1:c.2855delG NP_001393611.1:p.Ser952Metfs frameshift NM_001406683.1:c.2855delG NP_001393612.1:p.Ser952Metfs frameshift NM_001406684.1:c.2852delG NP_001393613.1:p.Ser951Metfs frameshift NM_001406685.1:c.2726delG NP_001393614.1:p.Ser909Metfs frameshift NM_001406686.1:c.2726delG NP_001393615.1:p.Ser909Metfs frameshift NM_001406687.1:c.2723delG NP_001393616.1:p.Ser908Metfs frameshift NM_001406688.1:c.2723delG NP_001393617.1:p.Ser908Metfs frameshift NM_001406689.1:c.2111delG NP_001393618.1:p.Ser704Metfs frameshift NM_001406690.1:c.1982delG NP_001393619.1:p.Ser661Metfs frameshift NM_001406691.1:c.1979delG NP_001393620.1:p.Ser660Metfs frameshift NM_001406692.1:c.1982delG NP_001393621.1:p.Ser661Metfs frameshift NM_001406693.1:c.1982delG NP_001393622.1:p.Ser661Metfs frameshift NM_001406694.1:c.1982delG NP_001393623.1:p.Ser661Metfs frameshift NM_001406695.1:c.1979delG NP_001393624.1:p.Ser660Metfs frameshift NM_001406696.1:c.1979delG NP_001393625.1:p.Ser660Metfs frameshift NM_001406697.1:c.1979delG NP_001393626.1:p.Ser660Metfs frameshift NM_001406698.1:c.1721delG NP_001393627.1:p.Ser574Metfs frameshift NM_021055.3:c.3326del NP_066399.2:p.Ser1109fs frameshift NR_176225.1:n.3476delG NR_176226.1:n.3655delG NR_176227.1:n.3652delG NR_176228.1:n.3473delG NR_176229.1:n.3433delG NC_000016.10:g.2080222del NC_000016.9:g.2130223del NG_005895.1:g.35917del LRG_487:g.35917del LRG_487t1:c.3455del LRG_487p1:p.Ser1152Metfs - Protein change
- S1108fs, S1152fs, S1072fs, S1119fs, S1109fs, S1060fs, S908fs
- Other names
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- Canonical SPDI
- NC_000016.10:2080221: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 |
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
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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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Apr 3, 2022 | RCV003048935.2 |
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
(Apr 03, 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: SCV003340901.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
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. … (more)
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 variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1152Metfs*39) 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 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.