ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1869del (p.Asp624fs)
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.1869del (p.Asp624fs)
Variation ID: 2802312 Accession: VCV002802312.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2071538 (GRCh38) [ NCBI UCSC ] 16: 2121539 (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 20, 2024 Feb 20, 2024 Nov 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.1869del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Asp624fs frameshift NM_001077183.3:c.1869del NP_001070651.1:p.Asp624fs frameshift NM_001114382.3:c.1869del NP_001107854.1:p.Asp624fs frameshift NM_001318827.2:c.1758del NP_001305756.1:p.Asp587fs frameshift NM_001318829.2:c.1722del NP_001305758.1:p.Asp575fs frameshift NM_001318831.2:c.1269del NP_001305760.1:p.Asp424fs frameshift NM_001318832.2:c.1902del NP_001305761.1:p.Asp635fs frameshift NM_001363528.2:c.1869del NP_001350457.1:p.Asp624fs frameshift NM_001370404.1:c.1869del NP_001357333.1:p.Asp624fs frameshift NM_001370405.1:c.1869del NP_001357334.1:p.Asp624fs frameshift NM_001406663.1:c.1869del NP_001393592.1:p.Asp624fs frameshift NM_001406664.1:c.1869del NP_001393593.1:p.Asp624fs frameshift NM_001406665.1:c.1869del NP_001393594.1:p.Asp624fs frameshift NM_001406667.1:c.1959del NP_001393596.1:p.Asp654fs frameshift NM_001406668.1:c.1959del NP_001393597.1:p.Asp654fs frameshift NM_001406670.1:c.1758del NP_001393599.1:p.Asp587fs frameshift NM_001406671.1:c.1857del NP_001393600.1:p.Asp620fs frameshift NM_001406673.1:c.1857del NP_001393602.1:p.Asp620fs frameshift NM_001406675.1:c.1722del NP_001393604.1:p.Asp575fs frameshift NM_001406676.1:c.1722del NP_001393605.1:p.Asp575fs frameshift NM_001406677.1:c.1812del NP_001393606.1:p.Asp605fs frameshift NM_001406678.1:c.1758del NP_001393607.1:p.Asp587fs frameshift NM_001406679.1:c.1722del NP_001393608.1:p.Asp575fs frameshift NM_001406680.1:c.1269del NP_001393609.1:p.Asp424fs frameshift NM_001406681.1:c.1407del NP_001393610.1:p.Asp470fs frameshift NM_001406682.1:c.1269del NP_001393611.1:p.Asp424fs frameshift NM_001406683.1:c.1269del NP_001393612.1:p.Asp424fs frameshift NM_001406684.1:c.1269del NP_001393613.1:p.Asp424fs frameshift NM_001406685.1:c.1269del NP_001393614.1:p.Asp424fs frameshift NM_001406686.1:c.1269del NP_001393615.1:p.Asp424fs frameshift NM_001406687.1:c.1269del NP_001393616.1:p.Asp424fs frameshift NM_001406688.1:c.1269del NP_001393617.1:p.Asp424fs frameshift NM_001406689.1:c.525del NP_001393618.1:p.Asp176fs frameshift NM_001406690.1:c.525del NP_001393619.1:p.Asp176fs frameshift NM_001406691.1:c.525del NP_001393620.1:p.Asp176fs frameshift NM_001406692.1:c.525del NP_001393621.1:p.Asp176fs frameshift NM_001406693.1:c.525del NP_001393622.1:p.Asp176fs frameshift NM_001406694.1:c.525del NP_001393623.1:p.Asp176fs frameshift NM_001406695.1:c.525del NP_001393624.1:p.Asp176fs frameshift NM_001406696.1:c.525del NP_001393625.1:p.Asp176fs frameshift NM_001406697.1:c.525del NP_001393626.1:p.Asp176fs frameshift NM_001406698.1:c.267del NP_001393627.1:p.Asp90fs frameshift NM_021055.3:c.1869del NP_066399.2:p.Asp624fs frameshift NR_176225.1:n.1979del non-coding transcript variant NR_176226.1:n.2198del non-coding transcript variant NR_176227.1:n.2198del non-coding transcript variant NR_176228.1:n.1979del non-coding transcript variant NR_176229.1:n.1979del non-coding transcript variant NC_000016.10:g.2071539del NC_000016.9:g.2121540del NG_005895.1:g.27234del LRG_487:g.27234del LRG_487t1:c.1869del LRG_487p1:p.Asp624Thrfs - Protein change
- D176fs, D424fs, D470fs, D624fs, D575fs, D635fs, D654fs, D605fs, D620fs, D90fs, D587fs
- Other names
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- Canonical SPDI
- NC_000016.10:2071537: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
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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
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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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Nov 10, 2023 | RCV003627696.1 |
Submissions - Germline
Classification
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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
(Nov 10, 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: SCV004401141.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp624Thrfs*74) 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.Asp624Thrfs*74) 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.