ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.2680del (p.His894fs)
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.2680del (p.His894fs)
Variation ID: 2035721 Accession: VCV002035721.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132897556 (GRCh38) [ NCBI UCSC ] 9: 135772943 (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 Oct 15, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000368.5:c.2680del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000359.1:p.His894fs frameshift NM_001162426.2:c.2677del NP_001155898.1:p.His893fs frameshift NM_001162427.2:c.2527del NP_001155899.1:p.His843fs frameshift NM_001362177.2:c.2317del NP_001349106.1:p.His773fs frameshift NM_001406592.1:c.2679delC NP_001393521.1:p.His894Metfs frameshift NM_001406593.1:c.2679delC NP_001393522.1:p.His894Metfs frameshift NM_001406594.1:c.2679delC NP_001393523.1:p.His894Metfs frameshift NM_001406595.1:c.2679delC NP_001393524.1:p.His894Metfs frameshift NM_001406596.1:c.2679delC NP_001393525.1:p.His894Metfs frameshift NM_001406597.1:c.2676delC NP_001393526.1:p.His893Metfs frameshift NM_001406598.1:c.2676delC NP_001393527.1:p.His893Metfs frameshift NM_001406599.1:c.2676delC NP_001393528.1:p.His893Metfs frameshift NM_001406600.1:c.2676delC NP_001393529.1:p.His893Metfs frameshift NM_001406601.1:c.2664delC NP_001393530.1:p.His889Metfs frameshift NM_001406602.1:c.2664delC NP_001393531.1:p.His889Metfs frameshift NM_001406603.1:c.2661delC NP_001393532.1:p.His888Metfs frameshift NM_001406604.1:c.2661delC NP_001393533.1:p.His888Metfs frameshift NM_001406605.1:c.2637delC NP_001393534.1:p.His880Metfs frameshift NM_001406606.1:c.2637delC NP_001393535.1:p.His880Metfs frameshift NM_001406607.1:c.2637delC NP_001393536.1:p.His880Metfs frameshift NM_001406608.1:c.2634delC NP_001393537.1:p.His879Metfs frameshift NM_001406609.1:c.2634delC NP_001393538.1:p.His879Metfs frameshift NM_001406610.1:c.2526delC NP_001393539.1:p.His843Metfs frameshift NM_001406611.1:c.2523delC NP_001393540.1:p.His842Metfs frameshift NM_001406612.1:c.2523delC NP_001393541.1:p.His842Metfs frameshift NM_001406613.1:c.2481delC NP_001393542.1:p.His828Metfs frameshift NM_001406614.1:c.2316delC NP_001393543.1:p.His773Metfs frameshift NM_001406615.1:c.2316delC NP_001393544.1:p.His773Metfs frameshift NM_001406616.1:c.2316delC NP_001393545.1:p.His773Metfs frameshift NM_001406617.1:c.2316delC NP_001393546.1:p.His773Metfs frameshift NM_001406618.1:c.2316delC NP_001393547.1:p.His773Metfs frameshift NM_001406619.1:c.2316delC NP_001393548.1:p.His773Metfs frameshift NM_001406620.1:c.2313delC NP_001393549.1:p.His772Metfs frameshift NM_001406621.1:c.2313delC NP_001393550.1:p.His772Metfs frameshift NM_001406622.1:c.2313delC NP_001393551.1:p.His772Metfs frameshift NM_001406623.1:c.2313delC NP_001393552.1:p.His772Metfs frameshift NM_001406624.1:c.2274delC NP_001393553.1:p.His759Metfs frameshift NM_001406625.1:c.2271delC NP_001393554.1:p.His758Metfs frameshift NM_001406626.1:c.1728delC NP_001393555.1:p.His577Metfs frameshift NM_001406627.1:c.1725delC NP_001393556.1:p.His576Metfs frameshift NM_001406628.1:c.1725delC NP_001393557.1:p.His576Metfs frameshift NM_001406629.1:c.1626delC NP_001393558.1:p.His543Metfs frameshift NM_001406630.1:c.1626delC NP_001393559.1:p.His543Metfs frameshift NR_176214.1:n.2729delC NR_176215.1:n.2896delC NR_176216.1:n.2763delC NR_176217.1:n.2893delC NR_176218.1:n.2892delC NC_000009.12:g.132897557del NC_000009.11:g.135772944del NG_012386.1:g.52078del LRG_486:g.52078del LRG_486t1:c.2679del LRG_486p1:p.His894Metfs - Protein change
- H843fs, H893fs, H894fs, H773fs
- Other names
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- Canonical SPDI
- NC_000009.12:132897555:GG: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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TSC1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4737 | 4786 |
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
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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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Oct 15, 2022 | RCV002894424.2 |
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
(Oct 15, 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: SCV003236935.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSC1-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TSC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His894Metfs*37) 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.