ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.1029+1G>A
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.1029+1G>A
Variation ID: 48729 Accession: VCV000048729.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132911452 (GRCh38) [ NCBI UCSC ] 9: 135786839 (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 Sep 16, 2013 May 1, 2024 Jan 15, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
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- Canonical SPDI
- NC_000009.12:132911451:C:T
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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 | ||
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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
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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TSC1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4839 | 4897 |
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
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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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not provided (1) |
no classification provided
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- | RCV000041976.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 15, 2024 | RCV001204448.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 8, 2022 | RCV002477137.1 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Nov 14, 2023 | RCV004018918.1 |
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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Pathogenic
(May 04, 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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Mendelics
Accession: SCV002519902.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Likely pathogenic
(Nov 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005034649.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.1029+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the TSC1 gene. This alteration was identified … (more)
The c.1029+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the TSC1 gene. This alteration was identified in 1 of 243 unrelated Chinese probands with a clinical diagnosis of TSC (Ding Y et al. Front Genet, 2020 Mar;11:204). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. (less)
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Pathogenic
(Mar 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 1
Lymphangiomyomatosis Isolated focal cortical dysplasia type II
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002781511.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 15, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001375654.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 10 of the TSC1 gene. RNA analysis indicates that disruption of this splice site induces … (more)
This sequence change affects a donor splice site in intron 10 of the TSC1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs118203485, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with tuberous sclerosis complex (PMID: 10533069; Invitae). ClinVar contains an entry for this variant (Variation ID: 48729). Studies have shown that disruption of this splice site results in inclusion of intron 10 and introduces a premature termination codon (PMID: 10533069). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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not provided
(-)
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no classification provided
Method: curation
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TSC
Affected status: yes
Allele origin:
germline
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Tuberous sclerosis database (TSC1)
Accession: SCV000065755.3
First in ClinVar: May 04, 2013 Last updated: Sep 16, 2013 |
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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 and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study. | Ding Y | Frontiers in genetics | 2020 | PMID: 32211034 |
Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations. | Bénit P | Human mutation | 1999 | PMID: 10533069 |
Text-mined citations for rs118203485 ...
HelpRecord last updated Sep 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.