A previously undescribed nucleotide variant creates a frameshift p.Val909CysfsTer6 in the TSC2 gene. The variant was observed in heterozygous state in an individual affected with tuberous sclerosis. Loss-of-function variants are reported in patients with Tuberous sclerosis-2, 613254. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.2724dup (p.Val909fs)
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)
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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.
Likely pathogenic
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.2724dup (p.Val909fs)
Variation ID: 3062291 Accession: VCV003062291.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2076148-2076149 (GRCh38) [ NCBI UCSC ] 16: 2126149-2126150 (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 23, 2024 Mar 23, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.2724dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Val909fs frameshift NM_001077183.3:c.2724dup NP_001070651.1:p.Val909fs frameshift NM_001114382.3:c.2724dup NP_001107854.1:p.Val909fs frameshift NM_001318827.2:c.2613dup NP_001305756.1:p.Val872fs frameshift NM_001318829.2:c.2577dup NP_001305758.1:p.Val860fs frameshift NM_001318831.2:c.2124dup NP_001305760.1:p.Val709fs frameshift NM_001318832.2:c.2757dup NP_001305761.1:p.Val920fs frameshift NM_001363528.2:c.2724dup NP_001350457.1:p.Val909fs frameshift NM_001370404.1:c.2724dup NP_001357333.1:p.Val909fs frameshift NM_001370405.1:c.2724dup NP_001357334.1:p.Val909fs frameshift NM_001406663.1:c.2724dup NP_001393592.1:p.Val909fs frameshift NM_001406664.1:c.2724dup NP_001393593.1:p.Val909fs frameshift NM_001406665.1:c.2724dup NP_001393594.1:p.Val909fs frameshift NM_001406667.1:c.2814dup NP_001393596.1:p.Val939fs frameshift NM_001406668.1:c.2814dup NP_001393597.1:p.Val939fs frameshift NM_001406670.1:c.2613dup NP_001393599.1:p.Val872fs frameshift NM_001406671.1:c.2712dup NP_001393600.1:p.Val905fs frameshift NM_001406673.1:c.2712dup NP_001393602.1:p.Val905fs frameshift NM_001406675.1:c.2577dup NP_001393604.1:p.Val860fs frameshift NM_001406676.1:c.2577dup NP_001393605.1:p.Val860fs frameshift NM_001406677.1:c.2667dup NP_001393606.1:p.Val890fs frameshift NM_001406678.1:c.2613dup NP_001393607.1:p.Val872fs frameshift NM_001406679.1:c.2577dup NP_001393608.1:p.Val860fs frameshift NM_001406680.1:c.2124dup NP_001393609.1:p.Val709fs frameshift NM_001406681.1:c.2262dup NP_001393610.1:p.Val755fs frameshift NM_001406682.1:c.2124dup NP_001393611.1:p.Val709fs frameshift NM_001406683.1:c.2124dup NP_001393612.1:p.Val709fs frameshift NM_001406684.1:c.2124dup NP_001393613.1:p.Val709fs frameshift NM_001406685.1:c.2124dup NP_001393614.1:p.Val709fs frameshift NM_001406686.1:c.2124dup NP_001393615.1:p.Val709fs frameshift NM_001406687.1:c.2124dup NP_001393616.1:p.Val709fs frameshift NM_001406688.1:c.2124dup NP_001393617.1:p.Val709fs frameshift NM_001406689.1:c.1380dup NP_001393618.1:p.Val461fs frameshift NM_001406690.1:c.1380dup NP_001393619.1:p.Val461fs frameshift NM_001406691.1:c.1380dup NP_001393620.1:p.Val461fs frameshift NM_001406692.1:c.1380dup NP_001393621.1:p.Val461fs frameshift NM_001406693.1:c.1380dup NP_001393622.1:p.Val461fs frameshift NM_001406694.1:c.1380dup NP_001393623.1:p.Val461fs frameshift NM_001406695.1:c.1380dup NP_001393624.1:p.Val461fs frameshift NM_001406696.1:c.1380dup NP_001393625.1:p.Val461fs frameshift NM_001406697.1:c.1380dup NP_001393626.1:p.Val461fs frameshift NM_001406698.1:c.1122dup NP_001393627.1:p.Val375fs frameshift NM_021055.3:c.2724dup NP_066399.2:p.Val909fs frameshift NR_176225.1:n.2874dup non-coding transcript variant NR_176226.1:n.3053dup non-coding transcript variant NR_176227.1:n.3053dup non-coding transcript variant NR_176228.1:n.2874dup non-coding transcript variant NR_176229.1:n.2834dup non-coding transcript variant NC_000016.10:g.2076152dup NC_000016.9:g.2126153dup NG_005895.1:g.31847dup LRG_487:g.31847dup LRG_487t1:c.2724dup LRG_487p1:p.Val909Cysfs - Protein change
- V375fs, V461fs, V709fs, V755fs, V860fs, V872fs, V890fs, V905fs, V909fs, V920fs, V939fs
- Other names
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- Canonical SPDI
- NC_000016.10:2076148:TTTT:TTTTT
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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. |
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| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10764 | 10963 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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- | RCV003986013.1 |
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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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: yes
Allele origin:
germline
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Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology
Accession: SCV004801844.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
A previously undescribed nucleotide variant creates a frameshift p.Val909CysfsTer6 in the TSC2 gene. The variant was observed in heterozygous state in an individual affected with … (more)
A previously undescribed nucleotide variant creates a frameshift p.Val909CysfsTer6 in the TSC2 gene. The variant was observed in heterozygous state in an individual affected with tuberous sclerosis. Loss-of-function variants are reported in patients with Tuberous sclerosis-2, 613254. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic. (less)
|
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:
A previously undescribed nucleotide variant creates a frameshift p.Val909CysfsTer6 in the TSC2 gene. The variant was observed in heterozygous state in an individual affected with tuberous sclerosis. Loss-of-function variants are reported in patients with Tuberous sclerosis-2, 613254. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.
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 30, 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.