ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4795del (p.Val1599fs)
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.4795del (p.Val1599fs)
Variation ID: 2861950 Accession: VCV002861950.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2086325 (GRCh38) [ NCBI UCSC ] 16: 2136326 (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 May 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4795del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Val1599fs frameshift NM_001077183.3:c.4594del NP_001070651.1:p.Val1532fs frameshift NM_001114382.3:c.4726del NP_001107854.1:p.Val1576fs frameshift NM_001318827.2:c.4486del NP_001305756.1:p.Val1496fs frameshift NM_001318829.2:c.4450del NP_001305758.1:p.Val1484fs frameshift NM_001318831.2:c.4063del NP_001305760.1:p.Val1355fs frameshift NM_001318832.2:c.4627del NP_001305761.1:p.Val1543fs frameshift NM_001363528.2:c.4597del NP_001350457.1:p.Val1533fs frameshift NM_001370404.1:c.4663del NP_001357333.1:p.Val1555fs frameshift NM_001370405.1:c.4666del NP_001357334.1:p.Val1556fs frameshift NM_001406663.1:c.4792del NP_001393592.1:p.Val1598fs frameshift NM_001406664.1:c.4723del NP_001393593.1:p.Val1575fs frameshift NM_001406665.1:c.4717del NP_001393594.1:p.Val1573fs frameshift NM_001406667.1:c.4687del NP_001393596.1:p.Val1563fs frameshift NM_001406668.1:c.4684del NP_001393597.1:p.Val1562fs frameshift NM_001406670.1:c.4615del NP_001393599.1:p.Val1539fs frameshift NM_001406671.1:c.4585del NP_001393600.1:p.Val1529fs frameshift NM_001406673.1:c.4582del NP_001393602.1:p.Val1528fs frameshift NM_001406675.1:c.4579del NP_001393604.1:p.Val1527fs frameshift NM_001406676.1:c.4576del NP_001393605.1:p.Val1526fs frameshift NM_001406677.1:c.4537del NP_001393606.1:p.Val1513fs frameshift NM_001406678.1:c.4483del NP_001393607.1:p.Val1495fs frameshift NM_001406679.1:c.4447del NP_001393608.1:p.Val1483fs frameshift NM_001406680.1:c.4195del NP_001393609.1:p.Val1399fs frameshift NM_001406681.1:c.4135del NP_001393610.1:p.Val1379fs frameshift NM_001406682.1:c.4126del NP_001393611.1:p.Val1376fs frameshift NM_001406683.1:c.4126del NP_001393612.1:p.Val1376fs frameshift NM_001406684.1:c.4123del NP_001393613.1:p.Val1375fs frameshift NM_001406685.1:c.3997del NP_001393614.1:p.Val1333fs frameshift NM_001406686.1:c.3997del NP_001393615.1:p.Val1333fs frameshift NM_001406687.1:c.3994del NP_001393616.1:p.Val1332fs frameshift NM_001406688.1:c.3994del NP_001393617.1:p.Val1332fs frameshift NM_001406689.1:c.3382del NP_001393618.1:p.Val1128fs frameshift NM_001406690.1:c.3322del NP_001393619.1:p.Val1108fs frameshift NM_001406691.1:c.3319del NP_001393620.1:p.Val1107fs frameshift NM_001406692.1:c.3253del NP_001393621.1:p.Val1085fs frameshift NM_001406693.1:c.3253del NP_001393622.1:p.Val1085fs frameshift NM_001406694.1:c.3253del NP_001393623.1:p.Val1085fs frameshift NM_001406695.1:c.3250del NP_001393624.1:p.Val1084fs frameshift NM_001406696.1:c.3250del NP_001393625.1:p.Val1084fs frameshift NM_001406697.1:c.3250del NP_001393626.1:p.Val1084fs frameshift NM_001406698.1:c.2992del NP_001393627.1:p.Val998fs frameshift NM_021055.3:c.4666del NP_066399.2:p.Val1556fs frameshift NR_176225.1:n.4747del non-coding transcript variant NR_176226.1:n.4995del non-coding transcript variant NR_176227.1:n.4923del non-coding transcript variant NR_176228.1:n.4744del non-coding transcript variant NR_176229.1:n.4704del non-coding transcript variant NC_000016.10:g.2086325del NC_000016.9:g.2136326del NG_005895.1:g.42020del LRG_487:g.42020del LRG_487t1:c.4795del LRG_487p1:p.Val1599Cysfs - Protein change
- V1332fs, V1333fs, V1376fs, V1399fs, V1496fs, V1527fs, V1563fs, V1575fs, V1576fs, V1084fs, V1085fs, V1107fs, V1128fs, V1379fs, V1484fs, V1528fs, V1532fs, V1543fs, V1562fs, V998fs, V1108fs, V1355fs, V1375fs, V1495fs, V1513fs, V1529fs, V1533fs, V1555fs, V1556fs, V1483fs, V1526fs, V1539fs, V1573fs, V1598fs, V1599fs
- Other names
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- Canonical SPDI
- NC_000016.10:2086324: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
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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May 4, 2023 | RCV003626248.1 |
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
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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
(May 04, 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: SCV004463429.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val1599Cysfs*26) 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.Val1599Cysfs*26) 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). 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. (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.