ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.2672dup (p.Asn891fs)
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.2672dup (p.Asn891fs)
Variation ID: 48989 Accession: VCV000048989.14
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132897563-132897564 (GRCh38) [ NCBI UCSC ] 9: 135772950-135772951 (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 Feb 20, 2024 Nov 7, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000368.5:c.2672dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000359.1:p.Asn891fs frameshift NM_000368.5:c.2672dupA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_000368.4:c.2672dupA NM_001162426.2:c.2669dup NP_001155898.1:p.Asn890fs frameshift NM_001162427.2:c.2519dup NP_001155899.1:p.Asn840fs frameshift NM_001362177.2:c.2309dup NP_001349106.1:p.Asn770fs frameshift NC_000009.12:g.132897570dup NC_000009.11:g.135772957dup NG_012386.1:g.52070dup LRG_486:g.52070dup - Protein change
- N840fs, N770fs, N890fs, N891fs
- Other names
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- Canonical SPDI
- NC_000009.12:132897563:TTTTTTT:TTTTTTTT
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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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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
Help
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 |
4613 | 4665 |
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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not provided (1) |
no classification provided
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- | RCV000042240.3 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 7, 2021 | RCV000550474.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 3, 2019 | RCV001016278.2 |
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
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002040697.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
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Pathogenic
(Apr 03, 2019)
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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: SCV001177216.3
First in ClinVar: Mar 16, 2020 Last updated: Nov 29, 2022 |
Comment:
The c.2672dupA pathogenic mutation, located in coding exon 19 of the TSC1 gene, results from a duplication of A at nucleotide position 2672, causing a … (more)
The c.2672dupA pathogenic mutation, located in coding exon 19 of the TSC1 gene, results from a duplication of A at nucleotide position 2672, causing a translational frameshift with a predicted alternate stop codon (p.N891Kfs*13). This alteration has been identified in multiple individuals diagnosed with tuberous sclerosis and has been reported as 2887insA and 2887-2888insA in the literature (Jones AC et al. Hum. Mol. Genet., 1997 Nov;6:2155-61; Young JM et al. Ann. Hum. Genet., 1998 May;62:203-13; Ali JB et al. J. Med. Genet., 1998 Dec;35:969-72; Dabora SL et al. Ann. Hum. Genet., 1998 Nov;62:491-504). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Aug 16, 2021)
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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: SCV000641590.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). For these reasons, this variant has been classified as Pathogenic. This variant has … (more)
Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with tuberous sclerosis complex (PMID: 9328481, 9803264, 9863590, 10363127). This variant is also known as 2887insA and 2887_2888insA in the literature. ClinVar contains an entry for this variant (Variation ID: 48989). This sequence change creates a premature translational stop signal (p.Asn891Lysfs*13) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). (less)
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Pathogenic
(Jun 09, 2020)
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no assertion criteria provided
Method: clinical testing
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Tuberous sclerosis 1
Affected status: yes
Allele origin:
germline
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Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University
Accession: SCV001370509.1
First in ClinVar: Jul 06, 2020 Last updated: Jul 06, 2020 |
Number of individuals with the variant: 3
Ethnicity/Population group: Japanese
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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: SCV000066026.3
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/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 |
Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE. | Dabora SL | Annals of human genetics | 1998 | PMID: 10363127 |
Mutations in the TSC1 gene account for a minority of patients with tuberous sclerosis. | Ali JB | Journal of medical genetics | 1998 | PMID: 9863590 |
A mutation screen of the TSC1 gene reveals 26 protein truncating mutations and 1 splice site mutation in a panel of 79 tuberous sclerosis patients. | Young JM | Annals of human genetics | 1998 | PMID: 9803264 |
Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. | Jones AC | Human molecular genetics | 1997 | PMID: 9328481 |
Text-mined citations for rs118203724 ...
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.