ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.2744dup (p.His915fs)
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_000368.5(TSC1):c.2744dup (p.His915fs)
Variation ID: 2100106 Accession: VCV002100106.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132897491-132897492 (GRCh38) [ NCBI UCSC ] 9: 135772878-135772879 (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 Feb 20, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000368.5:c.2744dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000359.1:p.His915fs frameshift NM_001162426.2:c.2741dup NP_001155898.1:p.His914fs frameshift NM_001162427.2:c.2591dup NP_001155899.1:p.His864fs frameshift NM_001362177.2:c.2381dup NP_001349106.1:p.His794fs frameshift NM_001406592.1:c.2744dup NP_001393521.1:p.His915Glnfs frameshift NM_001406593.1:c.2744dup NP_001393522.1:p.His915Glnfs frameshift NM_001406594.1:c.2744dup NP_001393523.1:p.His915Glnfs frameshift NM_001406595.1:c.2744dup NP_001393524.1:p.His915Glnfs frameshift NM_001406596.1:c.2744dup NP_001393525.1:p.His915Glnfs frameshift NM_001406597.1:c.2741dup NP_001393526.1:p.His914Glnfs frameshift NM_001406598.1:c.2741dup NP_001393527.1:p.His914Glnfs frameshift NM_001406599.1:c.2741dup NP_001393528.1:p.His914Glnfs frameshift NM_001406600.1:c.2741dup NP_001393529.1:p.His914Glnfs frameshift NM_001406601.1:c.2729dup NP_001393530.1:p.His910Glnfs frameshift NM_001406602.1:c.2729dup NP_001393531.1:p.His910Glnfs frameshift NM_001406603.1:c.2726dup NP_001393532.1:p.His909Glnfs frameshift NM_001406604.1:c.2726dup NP_001393533.1:p.His909Glnfs frameshift NM_001406605.1:c.2702dup NP_001393534.1:p.His901Glnfs frameshift NM_001406606.1:c.2702dup NP_001393535.1:p.His901Glnfs frameshift NM_001406607.1:c.2702dup NP_001393536.1:p.His901Glnfs frameshift NM_001406608.1:c.2699dup NP_001393537.1:p.His900Glnfs frameshift NM_001406609.1:c.2699dup NP_001393538.1:p.His900Glnfs frameshift NM_001406610.1:c.2591dup NP_001393539.1:p.His864Glnfs frameshift NM_001406611.1:c.2588dup NP_001393540.1:p.His863Glnfs frameshift NM_001406612.1:c.2588dup NP_001393541.1:p.His863Glnfs frameshift NM_001406613.1:c.2546dup NP_001393542.1:p.His849Glnfs frameshift NM_001406614.1:c.2381dup NP_001393543.1:p.His794Glnfs frameshift NM_001406615.1:c.2381dup NP_001393544.1:p.His794Glnfs frameshift NM_001406616.1:c.2381dup NP_001393545.1:p.His794Glnfs frameshift NM_001406617.1:c.2381dup NP_001393546.1:p.His794Glnfs frameshift NM_001406618.1:c.2381dup NP_001393547.1:p.His794Glnfs frameshift NM_001406619.1:c.2381dup NP_001393548.1:p.His794Glnfs frameshift NM_001406620.1:c.2378dup NP_001393549.1:p.His793Glnfs frameshift NM_001406621.1:c.2378dup NP_001393550.1:p.His793Glnfs frameshift NM_001406622.1:c.2378dup NP_001393551.1:p.His793Glnfs frameshift NM_001406623.1:c.2378dup NP_001393552.1:p.His793Glnfs frameshift NM_001406624.1:c.2339dup NP_001393553.1:p.His780Glnfs frameshift NM_001406625.1:c.2336dup NP_001393554.1:p.His779Glnfs frameshift NM_001406626.1:c.1793dup NP_001393555.1:p.His598Glnfs frameshift NM_001406627.1:c.1790dup NP_001393556.1:p.His597Glnfs frameshift NM_001406628.1:c.1790dup NP_001393557.1:p.His597Glnfs frameshift NM_001406629.1:c.1691dup NP_001393558.1:p.His564Glnfs frameshift NM_001406630.1:c.1691dup NP_001393559.1:p.His564Glnfs frameshift NR_176214.1:n.2794dup NR_176215.1:n.2961dup NR_176216.1:n.2828dup NR_176217.1:n.2958dup NR_176218.1:n.2957dup NC_000009.12:g.132897492dup NC_000009.11:g.135772879dup NG_012386.1:g.52142dup LRG_486:g.52142dup LRG_486t1:c.2744dup LRG_486p1:p.His915Glnfs - Protein change
- H864fs, H794fs, H914fs, H915fs
- Other names
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- Canonical SPDI
- NC_000009.12:132897491:T:TT
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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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TSC1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4614 | 4663 |
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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Feb 20, 2022 | RCV003014239.2 |
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
(Feb 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003319073.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This variant has not been reported in the literature in individuals affected with TSC1-related conditions. For these reasons, this variant has been classified as Pathogenic. … (more)
This variant has not been reported in the literature in individuals affected with TSC1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His915Glnfs*35) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 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 |
Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation. | van Slegtenhorst M | Journal of medical genetics | 1999 | PMID: 10227394 |
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.