This sequence change results in a frameshift in the TSC2 gene (p.Tyr1760Thrfs*66). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the TSC2 protein and extend the protein by 17 additional amino acid residues. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.5277del (p.Tyr1760fs)
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.
(1)
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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
1
criteria provided, single submitter
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.5277del (p.Tyr1760fs)
Variation ID: 2710601 Accession: VCV002710601.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088462 (GRCh38) [ NCBI UCSC ] 16: 2138463 (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 14, 2024 Feb 14, 2024 Jan 21, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.5277del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Tyr1760fs frameshift NM_001077183.3:c.5076del NP_001070651.1:p.Tyr1693fs frameshift NM_001114382.3:c.5208del NP_001107854.1:p.Tyr1737fs frameshift NM_001318827.2:c.4968del NP_001305756.1:p.Tyr1657fs frameshift NM_001318829.2:c.4932del NP_001305758.1:p.Tyr1645fs frameshift NM_001318831.2:c.4545del NP_001305760.1:p.Tyr1516fs frameshift NM_001318832.2:c.5109del NP_001305761.1:p.Tyr1704fs frameshift NM_001363528.2:c.5079del NP_001350457.1:p.Tyr1694fs frameshift NM_001370404.1:c.5145del NP_001357333.1:p.Tyr1716fs frameshift NM_001370405.1:c.5136del NP_001357334.1:p.Tyr1713fs frameshift NM_001406663.1:c.5274del NP_001393592.1:p.Tyr1759fs frameshift NM_001406664.1:c.5205del NP_001393593.1:p.Tyr1736fs frameshift NM_001406665.1:c.5199del NP_001393594.1:p.Tyr1734fs frameshift NM_001406667.1:c.5169del NP_001393596.1:p.Tyr1724fs frameshift NM_001406668.1:c.5166del NP_001393597.1:p.Tyr1723fs frameshift NM_001406670.1:c.5097del NP_001393599.1:p.Tyr1700fs frameshift NM_001406671.1:c.5067del NP_001393600.1:p.Tyr1690fs frameshift NM_001406673.1:c.5064del NP_001393602.1:p.Tyr1689fs frameshift NM_001406675.1:c.5061del NP_001393604.1:p.Tyr1688fs frameshift NM_001406676.1:c.5058del NP_001393605.1:p.Tyr1687fs frameshift NM_001406677.1:c.5019del NP_001393606.1:p.Tyr1674fs frameshift NM_001406678.1:c.4965del NP_001393607.1:p.Tyr1656fs frameshift NM_001406679.1:c.4929del NP_001393608.1:p.Tyr1644fs frameshift NM_001406680.1:c.4677del NP_001393609.1:p.Tyr1560fs frameshift NM_001406681.1:c.4617del NP_001393610.1:p.Tyr1540fs frameshift NM_001406682.1:c.4608del NP_001393611.1:p.Tyr1537fs frameshift NM_001406683.1:c.4608del NP_001393612.1:p.Tyr1537fs frameshift NM_001406684.1:c.4605del NP_001393613.1:p.Tyr1536fs frameshift NM_001406685.1:c.4479del NP_001393614.1:p.Tyr1494fs frameshift NM_001406686.1:c.4479del NP_001393615.1:p.Tyr1494fs frameshift NM_001406687.1:c.4476del NP_001393616.1:p.Tyr1493fs frameshift NM_001406688.1:c.4476del NP_001393617.1:p.Tyr1493fs frameshift NM_001406689.1:c.3864del NP_001393618.1:p.Tyr1289fs frameshift NM_001406690.1:c.3804del NP_001393619.1:p.Tyr1269fs frameshift NM_001406691.1:c.3801del NP_001393620.1:p.Tyr1268fs frameshift NM_001406692.1:c.3735del NP_001393621.1:p.Tyr1246fs frameshift NM_001406693.1:c.3735del NP_001393622.1:p.Tyr1246fs frameshift NM_001406694.1:c.3735del NP_001393623.1:p.Tyr1246fs frameshift NM_001406695.1:c.3732del NP_001393624.1:p.Tyr1245fs frameshift NM_001406696.1:c.3732del NP_001393625.1:p.Tyr1245fs frameshift NM_001406697.1:c.3732del NP_001393626.1:p.Tyr1245fs frameshift NM_001406698.1:c.3474del NP_001393627.1:p.Tyr1159fs frameshift NM_021055.3:c.5148del NP_066399.2:p.Tyr1717fs frameshift NR_176225.1:n.5229del non-coding transcript variant NR_176226.1:n.5477del non-coding transcript variant NR_176227.1:n.5405del non-coding transcript variant NR_176228.1:n.5226del non-coding transcript variant NR_176229.1:n.5151del non-coding transcript variant NC_000016.10:g.2088463del NC_000016.9:g.2138464del NG_005895.1:g.44158del NG_008617.1:g.54759del LRG_487:g.44158del LRG_487t1:c.5277del LRG_487p1:p.Tyr1760Thrfs - Protein change
- Y1656fs, Y1693fs, Y1694fs, Y1704fs, Y1713fs, Y1759fs, Y1245fs, Y1644fs, Y1289fs, Y1516fs, Y1657fs, Y1674fs, Y1688fs, Y1716fs, Y1723fs, Y1493fs, Y1494fs, Y1537fs, Y1689fs, Y1700fs, Y1736fs, Y1159fs, Y1246fs, Y1268fs, Y1269fs, Y1536fs, Y1540fs, Y1560fs, Y1645fs, Y1687fs, Y1690fs, Y1717fs, Y1724fs, Y1734fs, Y1737fs, Y1760fs
- Other names
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- Canonical SPDI
- NC_000016.10:2088461:CC:C
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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 |
10968 | 11169 | |
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 21, 2024 | RCV003513061.2 |
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
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 21, 2024)
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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: SCV004265155.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change results in a frameshift in the TSC2 gene (p.Tyr1760Thrfs*66). While this is not anticipated to result in nonsense mediated decay, it is … (more)
This sequence change results in a frameshift in the TSC2 gene (p.Tyr1760Thrfs*66). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the TSC2 protein and extend the protein by 17 additional amino acid residues. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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)
|
Comment:
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 sequence change results in a frameshift in the TSC2 gene (p.Tyr1760Thrfs*66). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the TSC2 protein and extend the protein by 17 additional amino acid residues. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
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 30, 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.