The variant is found in EPILEPSY,INFANT-EPI panel(s).
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4524CTT[1] (p.Phe1510del)
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.
(26)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(14); Likely benign(5)
Uncertain significance(1); Benign(14); Likely benign(5)
26
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000548.5(TSC2):c.4524CTT[1] (p.Phe1510del)
Variation ID: 49302 Accession: VCV000049302.57
- Type and length
-
Microsatellite, 3 bp
- Location
-
Cytogenetic: 16p13.3 16: 2084981-2084983 (GRCh38) [ NCBI UCSC ] 16: 2134985-2134987 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 12, 2013 Oct 20, 2024 Aug 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.4524CTT[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Phe1510del inframe deletion NM_000548.5:c.4527_4529del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000548.4:c.4527_4529delCTT NM_001077183.3:c.4323CTT[1] NP_001070651.1:p.Phe1443del inframe deletion NM_001114382.3:c.4455CTT[1] NP_001107854.1:p.Phe1487del inframe deletion NM_001318827.2:c.4215CTT[1] NP_001305756.1:p.Phe1407del inframe deletion NM_001318829.2:c.4179CTT[1] NP_001305758.1:p.Phe1395del inframe deletion NM_001318831.2:c.3792CTT[1] NP_001305760.1:p.Phe1266del inframe deletion NM_001318832.2:c.4356CTT[1] NP_001305761.1:p.Phe1454del inframe deletion NM_001363528.2:c.4326CTT[1] NP_001350457.1:p.Phe1444del inframe deletion NM_001370404.1:c.4392CTT[1] NP_001357333.1:p.Phe1466del inframe deletion NM_001370405.1:c.4395CTT[1] NP_001357334.1:p.Phe1467del inframe deletion NM_021055.3:c.4395CTT[1] NP_066399.2:p.Phe1467del inframe deletion NC_000016.10:g.2084981CTT[1] NC_000016.9:g.2134982CTT[1] NG_005895.1:g.40676CTT[1] LRG_487:g.40676CTT[1] LRG_487t1:c.4527_4529del - Protein change
- F1510del, F1467del, F1395del, F1407del, F1454del, F1466del, F1266del, F1443del, F1487del, F1444del
- Other names
- -
- Canonical SPDI
- NC_000016.10:2084980:CTTCTT:CTT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00399 (CTT)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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. |
|||
| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10745 | 10944 | |
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. |
|---|---|---|---|---|
| Benign/Likely benign (10) |
criteria provided, multiple submitters, no conflicts
|
Sep 24, 2022 | RCV000122238.34 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 24, 2020 | RCV000131063.14 | |
| Likely benign (3) |
criteria provided, single submitter
|
Jun 14, 2016 | RCV000042561.15 | |
| Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
|
Feb 1, 2024 | RCV000206029.27 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000034659.37 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Sep 30, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000243599.3
First in ClinVar: Aug 07, 2015 Last updated: Aug 07, 2015 |
Comment:
The variant is found in EPILEPSY,INFANT-EPI panel(s).
|
|
|
Likely benign
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous Sclerosis
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000395656.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Benign
(Mar 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540599.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.9% (155/16504) South Asian chromosomes. ClinVar: 3 labs classify as benign/likely benign (less)
Method: Genome/Exome Filtration
|
|
|
Benign
(May 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000677549.1
First in ClinVar: Jan 06, 2018 Last updated: Jan 06, 2018 |
|
|
|
Uncertain significance
(Nov 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: yes
Allele origin:
germline
|
Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000782412.1
First in ClinVar: May 26, 2018 Last updated: May 26, 2018 |
|
|
|
Benign
(Dec 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000229772.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Likely benign
(Jul 17, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Specified
Affected status: unknown
Allele origin:
germline
|
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
Accession: SCV000864295.1
First in ClinVar: Jan 22, 2019 Last updated: Jan 22, 2019 |
Comment:
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration … (more)
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). (less)
|
|
|
Likely benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139760.1
First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020 |
|
|
|
Benign
(Feb 14, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305224.2
First in ClinVar: Oct 02, 2016 Last updated: Dec 22, 2021 |
|
|
|
Benign
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002070009.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Feb 24, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002533939.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Likely benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545718.16
First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024 |
Comment:
TSC2: PM4:Supporting, BS2
Number of individuals with the variant: 93
|
|
|
Benign
(Jul 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000609596.1
First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
|
|
|
Likely benign
(Sep 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002598664.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
|
|
|
Benign
(Feb 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002774075.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Aug 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884753.5
First in ClinVar: May 30, 2018 Last updated: Mar 04, 2023 |
|
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016126.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
|
Benign
(Sep 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360920.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000262487.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Jul 20, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185993.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921709.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
probably not pathogenic
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043542.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Likely benign.
Number of individuals with the variant: 5
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808882.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000086461.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
|
|
not provided
(Apr 06, 2011)
|
no classification provided
Method: curation
|
not provided
Affected status: not provided
Allele origin:
not provided
|
Tuberous sclerosis database (TSC2)
Accession: SCV000066355.2
First in ClinVar: May 04, 2013 Last updated: Sep 22, 2013 |
|
|
|
not provided
(Apr 06, 2011)
|
no classification provided
Method: curation
|
not provided
Affected status: not provided
Allele origin:
not provided
|
Tuberous sclerosis database (TSC2)
Accession: SCV000066879.2
First in ClinVar: May 04, 2013 Last updated: Sep 22, 2013 |
|
|
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Comment:
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.9% (155/16504) South Asian chromosomes. ClinVar: 3 labs classify as benign/likely benign
Comment:
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Comment:
TSC2: PM4:Supporting, BS2
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Likely benign.
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 found in EPILEPSY,INFANT-EPI panel(s).
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.9% (155/16504) South Asian chromosomes. ClinVar: 3 labs classify as benign/likely benign
Comment:
BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Comment:
TSC2: PM4:Supporting, BS2
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Likely benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
| Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
| Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex. | Hoogeveen-Westerveld M | Human mutation | 2011 | PMID: 21309039 |
| Prenatal molecular diagnosis of tuberous sclerosis complex. | Milunsky A | American journal of obstetrics and gynecology | 2009 | PMID: 19254590 |
| 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 |
| Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. | Sancak O | European journal of human genetics : EJHG | 2005 | PMID: 15798777 |
| Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis. | Beauchamp RL | Human mutation | 1998 | PMID: 9829910 |
| The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. | Maheshwar MM | Human molecular genetics | 1997 | PMID: 9302281 |
| Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients. | Wilson PJ | Human molecular genetics | 1996 | PMID: 8824881 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TSC2 | - | - | - | - |
Text-mined citations for rs137854239 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 27, 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.