The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5280del (p.Ser1761fs)
Germline
Classification
Help
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.
(1)
Help
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.5280del (p.Ser1761fs)
Variation ID: 2444080 Accession: VCV002444080.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088466 (GRCh38) [ NCBI UCSC ] 16: 2138467 (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 Mar 18, 2023 Mar 18, 2023 Feb 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.5280del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ser1761fs frameshift NM_001077183.3:c.5079del NP_001070651.1:p.Ser1694fs frameshift NM_001114382.3:c.5211del NP_001107854.1:p.Ser1738fs frameshift NM_001318827.2:c.4971del NP_001305756.1:p.Ser1658fs frameshift NM_001318829.2:c.4935del NP_001305758.1:p.Ser1646fs frameshift NM_001318831.2:c.4548del NP_001305760.1:p.Ser1517fs frameshift NM_001318832.2:c.5112del NP_001305761.1:p.Ser1705fs frameshift NM_001363528.2:c.5082del NP_001350457.1:p.Ser1695fs frameshift NM_001370404.1:c.5148del NP_001357333.1:p.Ser1717fs frameshift NM_001370405.1:c.5139del NP_001357334.1:p.Ser1714fs frameshift NM_001406663.1:c.5277delC NP_001393592.1:p.Ser1760Profs frameshift NM_001406664.1:c.5208delC NP_001393593.1:p.Ser1737Profs frameshift NM_001406665.1:c.5202delC NP_001393594.1:p.Ser1735Profs frameshift NM_001406667.1:c.5172delC NP_001393596.1:p.Ser1725Profs frameshift NM_001406668.1:c.5169delC NP_001393597.1:p.Ser1724Profs frameshift NM_001406670.1:c.5100delC NP_001393599.1:p.Ser1701Profs frameshift NM_001406671.1:c.5070delC NP_001393600.1:p.Ser1691Profs frameshift NM_001406673.1:c.5067delC NP_001393602.1:p.Ser1690Profs frameshift NM_001406675.1:c.5064delC NP_001393604.1:p.Ser1689Profs frameshift NM_001406676.1:c.5061delC NP_001393605.1:p.Ser1688Profs frameshift NM_001406677.1:c.5022delC NP_001393606.1:p.Ser1675Profs frameshift NM_001406678.1:c.4968delC NP_001393607.1:p.Ser1657Profs frameshift NM_001406679.1:c.4932delC NP_001393608.1:p.Ser1645Profs frameshift NM_001406680.1:c.4680delC NP_001393609.1:p.Ser1561Profs frameshift NM_001406681.1:c.4620delC NP_001393610.1:p.Ser1541Profs frameshift NM_001406682.1:c.4611delC NP_001393611.1:p.Ser1538Profs frameshift NM_001406683.1:c.4611delC NP_001393612.1:p.Ser1538Profs frameshift NM_001406684.1:c.4608delC NP_001393613.1:p.Ser1537Profs frameshift NM_001406685.1:c.4482delC NP_001393614.1:p.Ser1495Profs frameshift NM_001406686.1:c.4482delC NP_001393615.1:p.Ser1495Profs frameshift NM_001406687.1:c.4479delC NP_001393616.1:p.Ser1494Profs frameshift NM_001406688.1:c.4479delC NP_001393617.1:p.Ser1494Profs frameshift NM_001406689.1:c.3867delC NP_001393618.1:p.Ser1290Profs frameshift NM_001406690.1:c.3807delC NP_001393619.1:p.Ser1270Profs frameshift NM_001406691.1:c.3804delC NP_001393620.1:p.Ser1269Profs frameshift NM_001406692.1:c.3738delC NP_001393621.1:p.Ser1247Profs frameshift NM_001406693.1:c.3738delC NP_001393622.1:p.Ser1247Profs frameshift NM_001406694.1:c.3738delC NP_001393623.1:p.Ser1247Profs frameshift NM_001406695.1:c.3735delC NP_001393624.1:p.Ser1246Profs frameshift NM_001406696.1:c.3735delC NP_001393625.1:p.Ser1246Profs frameshift NM_001406697.1:c.3735delC NP_001393626.1:p.Ser1246Profs frameshift NM_001406698.1:c.3477delC NP_001393627.1:p.Ser1160Profs frameshift NM_021055.3:c.5151del NP_066399.2:p.Ser1718fs frameshift NR_176225.1:n.5232delC NR_176226.1:n.5480delC NR_176227.1:n.5408delC NR_176228.1:n.5229delC NR_176229.1:n.5154delC NC_000016.10:g.2088466del NC_000016.9:g.2138467del NG_005895.1:g.44161del NG_008617.1:g.54755del LRG_487:g.44161del LRG_487t1:c.5280del LRG_487p1:p.Ser1761Profs - Protein change
- S1517fs, S1646fs, S1658fs, S1694fs, S1695fs, S1705fs, S1714fs, S1717fs, S1718fs, S1738fs, S1761fs
- Other names
- -
- Canonical SPDI
- NC_000016.10:2088465: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
Help
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
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 |
10758 | 10957 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 23, 2023 | RCV003152878.1 |
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. |
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|---|---|---|---|---|---|
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Uncertain significance
(Feb 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV003841367.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Seizure (present) , Abnormality of skin pigmentation (present)
|
Comment:
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. |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Mar 26, 2023
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.