ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4738dup (p.Arg1580fs)
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.4738dup (p.Arg1580fs)
Variation ID: 2842197 Accession: VCV002842197.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2136267-2136268 (GRCh37) [ NCBI UCSC ] 16: 2086266-2086267 (GRCh38) [ 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 20, 2024 Feb 20, 2024 Mar 2, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.4738dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Arg1580fs frameshift NM_001077183.3:c.4537dup NP_001070651.1:p.Arg1513fs frameshift NM_001114382.3:c.4669dup NP_001107854.1:p.Arg1557fs frameshift NM_001318827.2:c.4429dup NP_001305756.1:p.Arg1477fs frameshift NM_001318829.2:c.4393dup NP_001305758.1:p.Arg1465fs frameshift NM_001318831.2:c.4006dup NP_001305760.1:p.Arg1336fs frameshift NM_001318832.2:c.4570dup NP_001305761.1:p.Arg1524fs frameshift NM_001363528.2:c.4540dup NP_001350457.1:p.Arg1514fs frameshift NM_001370404.1:c.4606dup NP_001357333.1:p.Arg1536fs frameshift NM_001370405.1:c.4609dup NP_001357334.1:p.Arg1537fs frameshift NM_001406663.1:c.4735dup NP_001393592.1:p.Arg1579fs frameshift NM_001406664.1:c.4666dup NP_001393593.1:p.Arg1556fs frameshift NM_001406665.1:c.4660dup NP_001393594.1:p.Arg1554fs frameshift NM_001406667.1:c.4630dup NP_001393596.1:p.Arg1544fs frameshift NM_001406668.1:c.4627dup NP_001393597.1:p.Arg1543fs frameshift NM_001406670.1:c.4558dup NP_001393599.1:p.Arg1520fs frameshift NM_001406671.1:c.4528dup NP_001393600.1:p.Arg1510fs frameshift NM_001406673.1:c.4525dup NP_001393602.1:p.Arg1509fs frameshift NM_001406675.1:c.4522dup NP_001393604.1:p.Arg1508fs frameshift NM_001406676.1:c.4519dup NP_001393605.1:p.Arg1507fs frameshift NM_001406677.1:c.4480dup NP_001393606.1:p.Arg1494fs frameshift NM_001406678.1:c.4426dup NP_001393607.1:p.Arg1476fs frameshift NM_001406679.1:c.4390dup NP_001393608.1:p.Arg1464fs frameshift NM_001406680.1:c.4138dup NP_001393609.1:p.Arg1380fs frameshift NM_001406681.1:c.4078dup NP_001393610.1:p.Arg1360fs frameshift NM_001406682.1:c.4069dup NP_001393611.1:p.Arg1357fs frameshift NM_001406683.1:c.4069dup NP_001393612.1:p.Arg1357fs frameshift NM_001406684.1:c.4066dup NP_001393613.1:p.Arg1356fs frameshift NM_001406685.1:c.3940dup NP_001393614.1:p.Arg1314fs frameshift NM_001406686.1:c.3940dup NP_001393615.1:p.Arg1314fs frameshift NM_001406687.1:c.3937dup NP_001393616.1:p.Arg1313fs frameshift NM_001406688.1:c.3937dup NP_001393617.1:p.Arg1313fs frameshift NM_001406689.1:c.3325dup NP_001393618.1:p.Arg1109fs frameshift NM_001406690.1:c.3265dup NP_001393619.1:p.Arg1089fs frameshift NM_001406691.1:c.3262dup NP_001393620.1:p.Arg1088fs frameshift NM_001406692.1:c.3196dup NP_001393621.1:p.Arg1066fs frameshift NM_001406693.1:c.3196dup NP_001393622.1:p.Arg1066fs frameshift NM_001406694.1:c.3196dup NP_001393623.1:p.Arg1066fs frameshift NM_001406695.1:c.3193dup NP_001393624.1:p.Arg1065fs frameshift NM_001406696.1:c.3193dup NP_001393625.1:p.Arg1065fs frameshift NM_001406697.1:c.3193dup NP_001393626.1:p.Arg1065fs frameshift NM_001406698.1:c.2935dup NP_001393627.1:p.Arg979fs frameshift NM_021055.3:c.4609dup NP_066399.2:p.Arg1537fs frameshift NR_176225.1:n.4690dup non-coding transcript variant NR_176226.1:n.4938dup non-coding transcript variant NR_176227.1:n.4866dup non-coding transcript variant NR_176228.1:n.4687dup non-coding transcript variant NR_176229.1:n.4647dup non-coding transcript variant NC_000016.10:g.2086268dup NC_000016.9:g.2136269dup NG_005895.1:g.41963dup LRG_487:g.41963dup LRG_487t1:c.4738dup LRG_487p1:p.Arg1580Profs - Protein change
- R1065fs, R1088fs, R1336fs, R1357fs, R1380fs, R1509fs, R1513fs, R1514fs, R1543fs, R1314fs, R1465fs, R1477fs, R1507fs, R1508fs, R1089fs, R1313fs, R1360fs, R1494fs, R1520fs, R1524fs, R1544fs, R1556fs, R1557fs, R1580fs, R1554fs, R1579fs, R1066fs, R1109fs, R1356fs, R1464fs, R1476fs, R1510fs, R1536fs, R1537fs, R979fs
- Other names
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- Canonical SPDI
- NC_000016.10:2086266:CC:CCC
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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
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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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Mar 2, 2023 | RCV003628396.1 |
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
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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
(Mar 02, 2023)
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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: SCV004505487.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg1580Profs*23) in the TSC2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg1580Profs*23) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. For these reasons, this variant has been classified as Pathogenic. (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 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.