The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1659C>A (p.Tyr553Ter)
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)
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.
Likely pathogenic
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.1659C>A (p.Tyr553Ter)
Variation ID: 2444425 Accession: VCV002444425.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2065578 (GRCh38) [ NCBI UCSC ] 16: 2115579 (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 Mar 18, 2023 Mar 18, 2023 Feb 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.1659C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Tyr553Ter nonsense NM_001077183.3:c.1659C>A NP_001070651.1:p.Tyr553Ter nonsense NM_001114382.3:c.1659C>A NP_001107854.1:p.Tyr553Ter nonsense NM_001318827.2:c.1548C>A NP_001305756.1:p.Tyr516Ter nonsense NM_001318829.2:c.1512C>A NP_001305758.1:p.Tyr504Ter nonsense NM_001318831.2:c.1059C>A NP_001305760.1:p.Tyr353Ter nonsense NM_001318832.2:c.1692C>A NP_001305761.1:p.Tyr564Ter nonsense NM_001363528.2:c.1659C>A NP_001350457.1:p.Tyr553Ter nonsense NM_001370404.1:c.1659C>A NP_001357333.1:p.Tyr553Ter nonsense NM_001370405.1:c.1659C>A NP_001357334.1:p.Tyr553Ter nonsense NM_001406663.1:c.1659C>A NP_001393592.1:p.Tyr553Ter nonsense NM_001406664.1:c.1659C>A NP_001393593.1:p.Tyr553Ter nonsense NM_001406665.1:c.1659C>A NP_001393594.1:p.Tyr553Ter nonsense NM_001406667.1:c.1749C>A NP_001393596.1:p.Tyr583Ter nonsense NM_001406668.1:c.1749C>A NP_001393597.1:p.Tyr583Ter nonsense NM_001406670.1:c.1548C>A NP_001393599.1:p.Tyr516Ter nonsense NM_001406671.1:c.1647C>A NP_001393600.1:p.Tyr549Ter nonsense NM_001406673.1:c.1647C>A NP_001393602.1:p.Tyr549Ter nonsense NM_001406675.1:c.1512C>A NP_001393604.1:p.Tyr504Ter nonsense NM_001406676.1:c.1512C>A NP_001393605.1:p.Tyr504Ter nonsense NM_001406677.1:c.1602C>A NP_001393606.1:p.Tyr534Ter nonsense NM_001406678.1:c.1548C>A NP_001393607.1:p.Tyr516Ter nonsense NM_001406679.1:c.1512C>A NP_001393608.1:p.Tyr504Ter nonsense NM_001406680.1:c.1059C>A NP_001393609.1:p.Tyr353Ter nonsense NM_001406681.1:c.1197C>A NP_001393610.1:p.Tyr399Ter nonsense NM_001406682.1:c.1059C>A NP_001393611.1:p.Tyr353Ter nonsense NM_001406683.1:c.1059C>A NP_001393612.1:p.Tyr353Ter nonsense NM_001406684.1:c.1059C>A NP_001393613.1:p.Tyr353Ter nonsense NM_001406685.1:c.1059C>A NP_001393614.1:p.Tyr353Ter nonsense NM_001406686.1:c.1059C>A NP_001393615.1:p.Tyr353Ter nonsense NM_001406687.1:c.1059C>A NP_001393616.1:p.Tyr353Ter nonsense NM_001406688.1:c.1059C>A NP_001393617.1:p.Tyr353Ter nonsense NM_001406689.1:c.315C>A NP_001393618.1:p.Tyr105Ter nonsense NM_001406690.1:c.315C>A NP_001393619.1:p.Tyr105Ter nonsense NM_001406691.1:c.315C>A NP_001393620.1:p.Tyr105Ter nonsense NM_001406692.1:c.315C>A NP_001393621.1:p.Tyr105Ter nonsense NM_001406693.1:c.315C>A NP_001393622.1:p.Tyr105Ter nonsense NM_001406694.1:c.315C>A NP_001393623.1:p.Tyr105Ter nonsense NM_001406695.1:c.315C>A NP_001393624.1:p.Tyr105Ter nonsense NM_001406696.1:c.315C>A NP_001393625.1:p.Tyr105Ter nonsense NM_001406697.1:c.315C>A NP_001393626.1:p.Tyr105Ter nonsense NM_001406698.1:c.57C>A NP_001393627.1:p.Tyr19Ter nonsense NM_021055.3:c.1659C>A NP_066399.2:p.Tyr553Ter nonsense NR_176225.1:n.1769C>A NR_176226.1:n.1769C>A NR_176227.1:n.1769C>A NR_176228.1:n.1769C>A NR_176229.1:n.1769C>A NC_000016.10:g.2065578C>A NC_000016.9:g.2115579C>A NG_005895.1:g.21273C>A LRG_487:g.21273C>A LRG_487t1:c.1659C>A LRG_487p1:p.Tyr553Ter - Protein change
- Y105*, Y19*, Y353*, Y399*, Y504*, Y516*, Y534*, Y549*, Y553*, Y564*, Y583*
- Other names
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- Canonical SPDI
- NC_000016.10:2065577:C:A
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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 |
10758 | 10957 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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Feb 23, 2023 | RCV003153223.1 |
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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Likely pathogenic
(Feb 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV003842128.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Seizure (present) , Hypopigmented skin patches (present)
|
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:
The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
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 Mar 26, 2023
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.