The observed frameshift c.1831del(p.Ala611HisfsTer18) variant in TSC1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Ala611HisfsTer18 variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. This variant causes a frameshift starting with codon Alanine 611, changes this amino acid to Histidine residue, and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Ala611HisfsTer18. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000368.5(TSC1):c.1831del (p.Ala611fs)
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.
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_000368.5(TSC1):c.1831del (p.Ala611fs)
Variation ID: 3341409 Accession: VCV003341409.1
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 9q34.13 9: 132905747 (GRCh38) [ NCBI UCSC ] 9: 135781134 (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 Oct 8, 2024 Oct 8, 2024 May 20, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000368.5:c.1831del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000359.1:p.Ala611fs frameshift NM_001162426.2:c.1828del NP_001155898.1:p.Ala610fs frameshift NM_001162427.2:c.1678del NP_001155899.1:p.Ala560fs frameshift NM_001362177.2:c.1468del NP_001349106.1:p.Ala490fs frameshift NM_001406592.1:c.1831del NP_001393521.1:p.Ala611fs frameshift NM_001406593.1:c.1831del NP_001393522.1:p.Ala611fs frameshift NM_001406594.1:c.1831del NP_001393523.1:p.Ala611fs frameshift NM_001406595.1:c.1831del NP_001393524.1:p.Ala611fs frameshift NM_001406596.1:c.1831del NP_001393525.1:p.Ala611fs frameshift NM_001406597.1:c.1828del NP_001393526.1:p.Ala610fs frameshift NM_001406598.1:c.1828del NP_001393527.1:p.Ala610fs frameshift NM_001406599.1:c.1828del NP_001393528.1:p.Ala610fs frameshift NM_001406600.1:c.1828del NP_001393529.1:p.Ala610fs frameshift NM_001406601.1:c.1831del NP_001393530.1:p.Ala611fs frameshift NM_001406602.1:c.1831del NP_001393531.1:p.Ala611fs frameshift NM_001406603.1:c.1828del NP_001393532.1:p.Ala610fs frameshift NM_001406604.1:c.1828del NP_001393533.1:p.Ala610fs frameshift NM_001406605.1:c.1831del NP_001393534.1:p.Ala611fs frameshift NM_001406606.1:c.1831del NP_001393535.1:p.Ala611fs frameshift NM_001406607.1:c.1831del NP_001393536.1:p.Ala611fs frameshift NM_001406608.1:c.1828del NP_001393537.1:p.Ala610fs frameshift NM_001406609.1:c.1828del NP_001393538.1:p.Ala610fs frameshift NM_001406610.1:c.1678del NP_001393539.1:p.Ala560fs frameshift NM_001406611.1:c.1675del NP_001393540.1:p.Ala559fs frameshift NM_001406612.1:c.1675del NP_001393541.1:p.Ala559fs frameshift NM_001406613.1:c.1675del NP_001393542.1:p.Ala559fs frameshift NM_001406614.1:c.1468del NP_001393543.1:p.Ala490fs frameshift NM_001406615.1:c.1468del NP_001393544.1:p.Ala490fs frameshift NM_001406616.1:c.1468del NP_001393545.1:p.Ala490fs frameshift NM_001406617.1:c.1468del NP_001393546.1:p.Ala490fs frameshift NM_001406618.1:c.1468del NP_001393547.1:p.Ala490fs frameshift NM_001406619.1:c.1468del NP_001393548.1:p.Ala490fs frameshift NM_001406620.1:c.1465del NP_001393549.1:p.Ala489fs frameshift NM_001406621.1:c.1465del NP_001393550.1:p.Ala489fs frameshift NM_001406622.1:c.1465del NP_001393551.1:p.Ala489fs frameshift NM_001406623.1:c.1465del NP_001393552.1:p.Ala489fs frameshift NM_001406624.1:c.1468del NP_001393553.1:p.Ala490fs frameshift NM_001406625.1:c.1465del NP_001393554.1:p.Ala489fs frameshift NM_001406626.1:c.880del NP_001393555.1:p.Ala294fs frameshift NM_001406627.1:c.877del NP_001393556.1:p.Ala293fs frameshift NM_001406628.1:c.877del NP_001393557.1:p.Ala293fs frameshift NM_001406629.1:c.778del NP_001393558.1:p.Ala260fs frameshift NM_001406630.1:c.778del NP_001393559.1:p.Ala260fs frameshift NR_176214.1:n.2048del non-coding transcript variant NR_176215.1:n.2048del non-coding transcript variant NR_176216.1:n.1915del non-coding transcript variant NR_176217.1:n.2045del non-coding transcript variant NR_176218.1:n.2048del non-coding transcript variant NC_000009.12:g.132905748del NC_000009.11:g.135781135del NG_012386.1:g.43887del LRG_486:g.43887del LRG_486t1:c.1830del LRG_486p1:p.Ala611Hisfs - Protein change
- A260fs, A293fs, A294fs, A489fs, A490fs, A559fs, A560fs, A610fs, A611fs
- Other names
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- Canonical SPDI
- NC_000009.12:132905746: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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| TSC1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4844 | 4902 | |
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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May 20, 2023 | RCV004720667.1 |
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
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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
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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Likely pathogenic
(May 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005329491.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The observed frameshift c.1831del(p.Ala611HisfsTer18) variant in TSC1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The … (more)
The observed frameshift c.1831del(p.Ala611HisfsTer18) variant in TSC1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Ala611HisfsTer18 variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. This variant causes a frameshift starting with codon Alanine 611, changes this amino acid to Histidine residue, and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Ala611HisfsTer18. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. (less)
Clinical Features:
Abnormality of the nervous system (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 observed frameshift c.1831del(p.Ala611HisfsTer18) variant in TSC1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Ala611HisfsTer18 variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. This variant causes a frameshift starting with codon Alanine 611, changes this amino acid to Histidine residue, and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Ala611HisfsTer18. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
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 Oct 08, 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.