ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3326dup (p.Ala1110fs)
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.3326dup (p.Ala1110fs)
Variation ID: 3068623 Accession: VCV003068623.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2079596-2079597 (GRCh38) [ NCBI UCSC ] 16: 2129597-2129598 (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 Apr 15, 2024 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.3326dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ala1110fs frameshift NM_000548.5:c.3326dupC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_001077183.3:c.3194dup NP_001070651.1:p.Ala1066fs frameshift NM_001114382.3:c.3326dup NP_001107854.1:p.Ala1110fs frameshift NM_001318827.2:c.3086dup NP_001305756.1:p.Ala1030fs frameshift NM_001318829.2:c.3050dup NP_001305758.1:p.Ala1018fs frameshift NM_001318831.2:c.2594dup NP_001305760.1:p.Ala866fs frameshift NM_001318832.2:c.3227dup NP_001305761.1:p.Ala1077fs frameshift NM_001363528.2:c.3197dup NP_001350457.1:p.Ala1067fs frameshift NM_001370404.1:c.3194dup NP_001357333.1:p.Ala1066fs frameshift NM_001370405.1:c.3197dup NP_001357334.1:p.Ala1067fs frameshift NM_001406663.1:c.3323dup NP_001393592.1:p.Ala1109fs frameshift NM_001406664.1:c.3323dup NP_001393593.1:p.Ala1109fs frameshift NM_001406665.1:c.3194dup NP_001393594.1:p.Ala1066fs frameshift NM_001406667.1:c.3287dup NP_001393596.1:p.Ala1097fs frameshift NM_001406668.1:c.3284dup NP_001393597.1:p.Ala1096fs frameshift NM_001406670.1:c.3215dup NP_001393599.1:p.Ala1073fs frameshift NM_001406671.1:c.3185dup NP_001393600.1:p.Ala1063fs frameshift NM_001406673.1:c.3182dup NP_001393602.1:p.Ala1062fs frameshift NM_001406675.1:c.3179dup NP_001393604.1:p.Ala1061fs frameshift NM_001406676.1:c.3176dup NP_001393605.1:p.Ala1060fs frameshift NM_001406677.1:c.3137dup NP_001393606.1:p.Ala1047fs frameshift NM_001406678.1:c.3083dup NP_001393607.1:p.Ala1029fs frameshift NM_001406679.1:c.3047dup NP_001393608.1:p.Ala1017fs frameshift NM_001406680.1:c.2726dup NP_001393609.1:p.Ala910fs frameshift NM_001406681.1:c.2735dup NP_001393610.1:p.Ala913fs frameshift NM_001406682.1:c.2726dup NP_001393611.1:p.Ala910fs frameshift NM_001406683.1:c.2726dup NP_001393612.1:p.Ala910fs frameshift NM_001406684.1:c.2723dup NP_001393613.1:p.Ala909fs frameshift NM_001406685.1:c.2597dup NP_001393614.1:p.Ala867fs frameshift NM_001406686.1:c.2597dup NP_001393615.1:p.Ala867fs frameshift NM_001406687.1:c.2594dup NP_001393616.1:p.Ala866fs frameshift NM_001406688.1:c.2594dup NP_001393617.1:p.Ala866fs frameshift NM_001406689.1:c.1982dup NP_001393618.1:p.Ala662fs frameshift NM_001406690.1:c.1853dup NP_001393619.1:p.Ala619fs frameshift NM_001406691.1:c.1850dup NP_001393620.1:p.Ala618fs frameshift NM_001406692.1:c.1853dup NP_001393621.1:p.Ala619fs frameshift NM_001406693.1:c.1853dup NP_001393622.1:p.Ala619fs frameshift NM_001406694.1:c.1853dup NP_001393623.1:p.Ala619fs frameshift NM_001406695.1:c.1850dup NP_001393624.1:p.Ala618fs frameshift NM_001406696.1:c.1850dup NP_001393625.1:p.Ala618fs frameshift NM_001406697.1:c.1850dup NP_001393626.1:p.Ala618fs frameshift NM_001406698.1:c.1592dup NP_001393627.1:p.Ala532fs frameshift NM_021055.3:c.3197dup NP_066399.2:p.Ala1067fs frameshift NR_176225.1:n.3347dup non-coding transcript variant NR_176226.1:n.3526dup non-coding transcript variant NR_176227.1:n.3523dup non-coding transcript variant NR_176228.1:n.3344dup non-coding transcript variant NR_176229.1:n.3304dup non-coding transcript variant NC_000016.10:g.2079598dup NC_000016.9:g.2129599dup NG_005895.1:g.35293dup LRG_487:g.35293dup LRG_487t1:c.3326dup LRG_487p1:p.Ala1110Glyfs - Protein change
- A1017fs, A1018fs, A1029fs, A1030fs, A1047fs, A1060fs, A1061fs, A1062fs, A1063fs, A1066fs, A1067fs, A1073fs, A1077fs, A1096fs, A1097fs, A1109fs, A1110fs, A532fs, A618fs, A619fs, A662fs, A866fs, A867fs, A909fs, A910fs, A913fs
- Other names
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- Canonical SPDI
- NC_000016.10:2079596: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 1, 2024 | RCV003994692.1 |
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 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812656.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
This sequence change in TSC2 is a frameshift variant predicted to cause a premature stop codon, p.(Ala1110Glyfs*58), in biologically relevant exon 30/42 leading to nonsense-mediated … (more)
This sequence change in TSC2 is a frameshift variant predicted to cause a premature stop codon, p.(Ala1110Glyfs*58), in biologically relevant exon 30/42 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. This variant is absent from the population database gnomAD v4.0. To our knowledge, this variant is novel and has not been previously reported in the relevant scientific literature or databases. Mosaicism of this variant has been detected in an individual with a clinical diagnosis of tuberous sclerosis complex (this laboratory). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PS4_Supporting. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Apr 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.