ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.2265_2268del (p.Glu755fs)
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
-
NM_000548.5(TSC2):c.2265_2268del (p.Glu755fs)
Variation ID: 2710533 Accession: VCV002710533.2
- Type and length
-
Deletion, 4 bp
- Location
-
Cytogenetic: 16p13.3 16: 2072893-2072896 (GRCh38) [ NCBI UCSC ] 16: 2122894-2122897 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 15, 2024 Feb 14, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000548.5:c.2265_2268del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Glu755fs frameshift NM_000548.5:c.2265_2268delAGGC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001077183.3:c.2265_2268del NP_001070651.1:p.Glu755fs frameshift NM_001114382.3:c.2265_2268del NP_001107854.1:p.Glu755fs frameshift NM_001318827.2:c.2154_2157del NP_001305756.1:p.Glu718fs frameshift NM_001318829.2:c.2118_2121del NP_001305758.1:p.Glu706fs frameshift NM_001318831.2:c.1665_1668del NP_001305760.1:p.Glu555fs frameshift NM_001318832.2:c.2298_2301del NP_001305761.1:p.Glu766fs frameshift NM_001363528.2:c.2265_2268del NP_001350457.1:p.Glu755fs frameshift NM_001370404.1:c.2265_2268del NP_001357333.1:p.Glu755fs frameshift NM_001370405.1:c.2265_2268del NP_001357334.1:p.Glu755fs frameshift NM_001406663.1:c.2265_2268del NP_001393592.1:p.Glu755fs frameshift NM_001406664.1:c.2265_2268del NP_001393593.1:p.Glu755fs frameshift NM_001406665.1:c.2265_2268del NP_001393594.1:p.Glu755fs frameshift NM_001406667.1:c.2355_2358del NP_001393596.1:p.Glu785fs frameshift NM_001406668.1:c.2355_2358del NP_001393597.1:p.Glu785fs frameshift NM_001406670.1:c.2154_2157del NP_001393599.1:p.Glu718fs frameshift NM_001406671.1:c.2253_2256del NP_001393600.1:p.Glu751fs frameshift NM_001406673.1:c.2253_2256del NP_001393602.1:p.Glu751fs frameshift NM_001406675.1:c.2118_2121del NP_001393604.1:p.Glu706fs frameshift NM_001406676.1:c.2118_2121del NP_001393605.1:p.Glu706fs frameshift NM_001406677.1:c.2208_2211del NP_001393606.1:p.Glu736fs frameshift NM_001406678.1:c.2154_2157del NP_001393607.1:p.Glu718fs frameshift NM_001406679.1:c.2118_2121del NP_001393608.1:p.Glu706fs frameshift NM_001406680.1:c.1665_1668del NP_001393609.1:p.Glu555fs frameshift NM_001406681.1:c.1803_1806del NP_001393610.1:p.Glu601fs frameshift NM_001406682.1:c.1665_1668del NP_001393611.1:p.Glu555fs frameshift NM_001406683.1:c.1665_1668del NP_001393612.1:p.Glu555fs frameshift NM_001406684.1:c.1665_1668del NP_001393613.1:p.Glu555fs frameshift NM_001406685.1:c.1665_1668del NP_001393614.1:p.Glu555fs frameshift NM_001406686.1:c.1665_1668del NP_001393615.1:p.Glu555fs frameshift NM_001406687.1:c.1665_1668del NP_001393616.1:p.Glu555fs frameshift NM_001406688.1:c.1665_1668del NP_001393617.1:p.Glu555fs frameshift NM_001406689.1:c.921_924del NP_001393618.1:p.Glu307fs frameshift NM_001406690.1:c.921_924del NP_001393619.1:p.Glu307fs frameshift NM_001406691.1:c.921_924del NP_001393620.1:p.Glu307fs frameshift NM_001406692.1:c.921_924del NP_001393621.1:p.Glu307fs frameshift NM_001406693.1:c.921_924del NP_001393622.1:p.Glu307fs frameshift NM_001406694.1:c.921_924del NP_001393623.1:p.Glu307fs frameshift NM_001406695.1:c.921_924del NP_001393624.1:p.Glu307fs frameshift NM_001406696.1:c.921_924del NP_001393625.1:p.Glu307fs frameshift NM_001406697.1:c.921_924del NP_001393626.1:p.Glu307fs frameshift NM_001406698.1:c.663_666del NP_001393627.1:p.Glu221fs frameshift NM_021055.3:c.2265_2268del NP_066399.2:p.Glu755fs frameshift NR_176225.1:n.2415_2418del non-coding transcript variant NR_176226.1:n.2594_2597del non-coding transcript variant NR_176227.1:n.2594_2597del non-coding transcript variant NR_176228.1:n.2415_2418del non-coding transcript variant NR_176229.1:n.2375_2378del non-coding transcript variant NC_000016.10:g.2072893_2072896del NC_000016.9:g.2122894_2122897del NG_005895.1:g.28588_28591del LRG_487:g.28588_28591del LRG_487t1:c.2265_2268del LRG_487p1:p.Glu755Aspfs - Protein change
- E221fs, E555fs, E706fs, E736fs, E751fs, E307fs, E718fs, E766fs, E601fs, E755fs, E785fs
- Other names
- -
- Canonical SPDI
- NC_000016.10:2072892:AGGC:
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10625 | 10800 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Jan 21, 2024 | RCV003513059.1 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 14, 2024 | RCV003994567.1 |
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
Help
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
Help
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. |
|
---|---|---|---|---|---|
Pathogenic
(Jan 21, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV004264780.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu755Aspfs*15) 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.Glu755Aspfs*15) 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. 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)
|
|
Pathogenic
(Feb 14, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004813667.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
Variant summary: TSC2 c.2265_2268delAGGC (p.Glu755AspfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: TSC2 c.2265_2268delAGGC (p.Glu755AspfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251046 control chromosomes. To our knowledge, no occurrence of c.2265_2268delAGGC in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
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 |
---|---|---|---|---|
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 Jun 02, 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.