ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4404_4407dup (p.Arg1470fs)
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_000548.5(TSC2):c.4404_4407dup (p.Arg1470fs)
Variation ID: 2124298 Accession: VCV002124298.2
- Type and length
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Duplication, 4 bp
- Location
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Cytogenetic: 16p13.3 16: 2084625-2084626 (GRCh38) [ NCBI UCSC ] 16: 2134626-2134627 (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 Apr 10, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4404_4407dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Arg1470fs frameshift NM_001077183.3:c.4203_4206dup NP_001070651.1:p.Arg1403fs frameshift NM_001114382.3:c.4335_4338dup NP_001107854.1:p.Arg1447fs frameshift NM_001318827.2:c.4095_4098dup NP_001305756.1:p.Arg1367fs frameshift NM_001318829.2:c.4059_4062dup NP_001305758.1:p.Arg1355fs frameshift NM_001318831.2:c.3672_3675dup NP_001305760.1:p.Arg1226fs frameshift NM_001318832.2:c.4236_4239dup NP_001305761.1:p.Arg1414fs frameshift NM_001363528.2:c.4206_4209dup NP_001350457.1:p.Arg1404fs frameshift NM_001370404.1:c.4272_4275dup NP_001357333.1:p.Arg1426fs frameshift NM_001370405.1:c.4275_4278dup NP_001357334.1:p.Arg1427fs frameshift NM_001406663.1:c.4401_4404dup NP_001393592.1:p.Arg1469Ilefs frameshift NM_001406664.1:c.4332_4335dup NP_001393593.1:p.Arg1446Ilefs frameshift NM_001406665.1:c.4326_4329dup NP_001393594.1:p.Arg1444Ilefs frameshift NM_001406667.1:c.4296_4299dup NP_001393596.1:p.Arg1434Ilefs frameshift NM_001406668.1:c.4293_4296dup NP_001393597.1:p.Arg1433Ilefs frameshift NM_001406670.1:c.4224_4227dup NP_001393599.1:p.Arg1410Ilefs frameshift NM_001406671.1:c.4194_4197dup NP_001393600.1:p.Arg1400Ilefs frameshift NM_001406673.1:c.4191_4194dup NP_001393602.1:p.Arg1399Ilefs frameshift NM_001406675.1:c.4188_4191dup NP_001393604.1:p.Arg1398Ilefs frameshift NM_001406676.1:c.4185_4188dup NP_001393605.1:p.Arg1397Ilefs frameshift NM_001406677.1:c.4146_4149dup NP_001393606.1:p.Arg1384Ilefs frameshift NM_001406678.1:c.4092_4095dup NP_001393607.1:p.Arg1366Ilefs frameshift NM_001406679.1:c.4056_4059dup NP_001393608.1:p.Arg1354Ilefs frameshift NM_001406680.1:c.3804_3807dup NP_001393609.1:p.Arg1270Ilefs frameshift NM_001406681.1:c.3744_3747dup NP_001393610.1:p.Arg1250Ilefs frameshift NM_001406682.1:c.3735_3738dup NP_001393611.1:p.Arg1247Ilefs frameshift NM_001406683.1:c.3735_3738dup NP_001393612.1:p.Arg1247Ilefs frameshift NM_001406684.1:c.3732_3735dup NP_001393613.1:p.Arg1246Ilefs frameshift NM_001406685.1:c.3606_3609dup NP_001393614.1:p.Arg1204Ilefs frameshift NM_001406686.1:c.3606_3609dup NP_001393615.1:p.Arg1204Ilefs frameshift NM_001406687.1:c.3603_3606dup NP_001393616.1:p.Arg1203Ilefs frameshift NM_001406688.1:c.3603_3606dup NP_001393617.1:p.Arg1203Ilefs frameshift NM_001406689.1:c.2991_2994dup NP_001393618.1:p.Arg999Ilefs frameshift NM_001406690.1:c.2931_2934dup NP_001393619.1:p.Arg979Ilefs frameshift NM_001406691.1:c.2928_2931dup NP_001393620.1:p.Arg978Ilefs frameshift NM_001406692.1:c.2862_2865dup NP_001393621.1:p.Arg956Ilefs frameshift NM_001406693.1:c.2862_2865dup NP_001393622.1:p.Arg956Ilefs frameshift NM_001406694.1:c.2862_2865dup NP_001393623.1:p.Arg956Ilefs frameshift NM_001406695.1:c.2859_2862dup NP_001393624.1:p.Arg955Ilefs frameshift NM_001406696.1:c.2859_2862dup NP_001393625.1:p.Arg955Ilefs frameshift NM_001406697.1:c.2859_2862dup NP_001393626.1:p.Arg955Ilefs frameshift NM_001406698.1:c.2601_2604dup NP_001393627.1:p.Arg869Ilefs frameshift NM_021055.3:c.4275_4278dup NP_066399.2:p.Arg1427fs frameshift NR_176225.1:n.4356_4359dup NR_176226.1:n.4604_4607dup NR_176227.1:n.4532_4535dup NR_176228.1:n.4353_4356dup NR_176229.1:n.4313_4316dup NC_000016.10:g.2084626_2084629dup NC_000016.9:g.2134627_2134630dup NG_005895.1:g.40321_40324dup LRG_487:g.40321_40324dup LRG_487t1:c.4404_4407dup LRG_487p1:p.Arg1470Ilefs - Protein change
- R1226fs, R1367fs, R1426fs, R1447fs, R1403fs, R1404fs, R1355fs, R1414fs, R1427fs, R1470fs
- Other names
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- Canonical SPDI
- NC_000016.10:2084625:ATCA:ATCAATCA
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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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TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10625 | 10800 |
Conditions - Germline
Condition
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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
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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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Apr 10, 2022 | RCV003057091.2 |
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
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
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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
(Apr 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003343673.2
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 TSC2-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 TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1470Ilefs*55) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 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 |
Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. | Jones AC | American journal of human genetics | 1999 | PMID: 10205261 |
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.