This variant, c.5389_5391dup, results in the insertion of 1 amino acid(s) of the TSC2 protein (p.Ile1797dup), but otherwise preserves the integrity of the reading frame. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5389_5391dup (p.Ile1797_Ser1798insIle)
Germline
Classification
Help
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.
(2)
Help
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.5389_5391dup (p.Ile1797_Ser1798insIle)
Variation ID: 1977864 Accession: VCV001977864.3
- Type and length
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Duplication, 3 bp
- Location
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Cytogenetic: 16p13.3 16: 2088572-2088573 (GRCh38) [ NCBI UCSC ] 16: 2138573-2138574 (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 7, 2023 Aug 11, 2024 Apr 12, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.5389_5391dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ile1797_Ser1798insIle inframe insertion NM_000548.3:c.5389_5391dupATC NM_001077183.3:c.5188_5190dup NP_001070651.1:p.Ile1730_Ser1731insIle inframe insertion NM_001114382.3:c.5320_5322dup NP_001107854.1:p.Ile1774_Ser1775insIle inframe insertion NM_001318827.2:c.5080_5082dup NP_001305756.1:p.Ile1694_Ser1695insIle inframe insertion NM_001318829.2:c.5044_5046dup NP_001305758.1:p.Ile1682_Ser1683insIle inframe insertion NM_001318831.2:c.4657_4659dup NP_001305760.1:p.Ile1553_Ser1554insIle inframe insertion NM_001318832.2:c.5221_5223dup NP_001305761.1:p.Ile1741_Ser1742insIle inframe insertion NM_001363528.2:c.5191_5193dup NP_001350457.1:p.Ile1731_Ser1732insIle inframe insertion NM_001370404.1:c.5257_5259dup NP_001357333.1:p.Ile1753_Ser1754insIle inframe insertion NM_001370405.1:c.5248_5250dup NP_001357334.1:p.Ile1750_Ser1751insIle inframe insertion NM_001406663.1:c.5386_5388dup NP_001393592.1:p.Ile1796_Ser1797insIle inframe indel NM_001406664.1:c.5317_5319dup NP_001393593.1:p.Ile1773_Ser1774insIle inframe indel NM_001406665.1:c.5311_5313dup NP_001393594.1:p.Ile1771_Ser1772insIle inframe indel NM_001406667.1:c.5281_5283dup NP_001393596.1:p.Ile1761_Ser1762insIle inframe indel NM_001406668.1:c.5278_5280dup NP_001393597.1:p.Ile1760_Ser1761insIle inframe indel NM_001406670.1:c.5209_5211dup NP_001393599.1:p.Ile1737_Ser1738insIle inframe indel NM_001406671.1:c.5179_5181dup NP_001393600.1:p.Ile1727_Ser1728insIle inframe indel NM_001406673.1:c.5176_5178dup NP_001393602.1:p.Ile1726_Ser1727insIle inframe indel NM_001406675.1:c.5173_5175dup NP_001393604.1:p.Ile1725_Ser1726insIle inframe indel NM_001406676.1:c.5170_5172dup NP_001393605.1:p.Ile1724_Ser1725insIle inframe indel NM_001406677.1:c.5131_5133dup NP_001393606.1:p.Ile1711_Ser1712insIle inframe indel NM_001406678.1:c.5077_5079dup NP_001393607.1:p.Ile1693_Ser1694insIle inframe indel NM_001406679.1:c.5041_5043dup NP_001393608.1:p.Ile1681_Ser1682insIle inframe indel NM_001406680.1:c.4789_4791dup NP_001393609.1:p.Ile1597_Ser1598insIle inframe indel NM_001406681.1:c.4729_4731dup NP_001393610.1:p.Ile1577_Ser1578insIle inframe indel NM_001406682.1:c.4720_4722dup NP_001393611.1:p.Ile1574_Ser1575insIle inframe indel NM_001406683.1:c.4720_4722dup NP_001393612.1:p.Ile1574_Ser1575insIle inframe indel NM_001406684.1:c.4717_4719dup NP_001393613.1:p.Ile1573_Ser1574insIle inframe indel NM_001406685.1:c.4591_4593dup NP_001393614.1:p.Ile1531_Ser1532insIle inframe indel NM_001406686.1:c.4591_4593dup NP_001393615.1:p.Ile1531_Ser1532insIle inframe indel NM_001406687.1:c.4588_4590dup NP_001393616.1:p.Ile1530_Ser1531insIle inframe indel NM_001406688.1:c.4588_4590dup NP_001393617.1:p.Ile1530_Ser1531insIle inframe indel NM_001406689.1:c.3976_3978dup NP_001393618.1:p.Ile1326_Ser1327insIle inframe indel NM_001406690.1:c.3916_3918dup NP_001393619.1:p.Ile1306_Ser1307insIle inframe indel NM_001406691.1:c.3913_3915dup NP_001393620.1:p.Ile1305_Ser1306insIle inframe indel NM_001406692.1:c.3847_3849dup NP_001393621.1:p.Ile1283_Ser1284insIle inframe indel NM_001406693.1:c.3847_3849dup NP_001393622.1:p.Ile1283_Ser1284insIle inframe indel NM_001406694.1:c.3847_3849dup NP_001393623.1:p.Ile1283_Ser1284insIle inframe indel NM_001406695.1:c.3844_3846dup NP_001393624.1:p.Ile1282_Ser1283insIle inframe indel NM_001406696.1:c.3844_3846dup NP_001393625.1:p.Ile1282_Ser1283insIle inframe indel NM_001406697.1:c.3844_3846dup NP_001393626.1:p.Ile1282_Ser1283insIle inframe indel NM_001406698.1:c.3586_3588dup NP_001393627.1:p.Ile1196_Ser1197insIle inframe indel NM_021055.3:c.5260_5262dup NP_066399.2:p.Ile1754_Ser1755insIle inframe insertion NR_176225.1:n.5341_5343dup NR_176226.1:n.5589_5591dup NR_176227.1:n.5517_5519dup NR_176228.1:n.5338_5340dup NR_176229.1:n.5263_5265dup NC_000016.10:g.2088575_2088577dup NC_000016.9:g.2138576_2138578dup NG_005895.1:g.44270_44272dup NG_008617.1:g.54646_54648dup LRG_487:g.44270_44272dup LRG_487t1:c.5389_5391dup LRG_487p1:p.Ile1797_Ser1798insIle - Protein change
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- Other names
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- Canonical SPDI
- NC_000016.10:2088572:TCATC:TCATCATC
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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
Help
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
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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
Help
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 |
10752 | 10951 | |
Conditions - Germline
| Condition
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Jan 15, 2022 | RCV002736837.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Apr 12, 2024 | RCV004681544.1 |
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
Help
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
Help
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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|---|---|---|---|---|---|
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Uncertain significance
(Jan 15, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003012804.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This variant, c.5389_5391dup, results in the insertion of 1 amino acid(s) of the TSC2 protein (p.Ile1797dup), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.5389_5391dup, results in the insertion of 1 amino acid(s) of the TSC2 protein (p.Ile1797dup), but otherwise preserves the integrity of the reading frame. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
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Uncertain significance
(Apr 12, 2024)
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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: SCV005174598.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
The c.5389_5391dupATC variant (also known as p.I1797dup), located in coding exon 41 of the TSC2 gene, results from an in-frame duplication of ATC at nucleotide … (more)
The c.5389_5391dupATC variant (also known as p.I1797dup), located in coding exon 41 of the TSC2 gene, results from an in-frame duplication of ATC at nucleotide positions 5389 to 5391. This results in the duplication of an extra residue between codons 1797 and 1798. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear. (less)
|
Comment:
Comment:
The c.5389_5391dupATC variant (also known as p.I1797dup), located in coding exon 41 of the TSC2 gene, results from an in-frame duplication of ATC at nucleotide positions 5389 to 5391. This results in the duplication of an extra residue between codons 1797 and 1798. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.
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. |
Comment:
This variant, c.5389_5391dup, results in the insertion of 1 amino acid(s) of the TSC2 protein (p.Ile1797dup), but otherwise preserves the integrity of the reading frame. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The c.5389_5391dupATC variant (also known as p.I1797dup), located in coding exon 41 of the TSC2 gene, results from an in-frame duplication of ATC at nucleotide positions 5389 to 5391. This results in the duplication of an extra residue between codons 1797 and 1798. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.
Citations for germline classification of this variant
Help| There 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 Sep 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.