ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys)
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
-
NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys)
Variation ID: 41748 Accession: VCV000041748.64
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2088569 (GRCh38) [ NCBI UCSC ] 16: 2138570 (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 May 1, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000548.5:c.5383C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Arg1795Cys missense NM_001077183.3:c.5182C>T NP_001070651.1:p.Arg1728Cys missense NM_001114382.3:c.5314C>T NP_001107854.1:p.Arg1772Cys missense NM_001318827.2:c.5074C>T NP_001305756.1:p.Arg1692Cys missense NM_001318829.2:c.5038C>T NP_001305758.1:p.Arg1680Cys missense NM_001318831.2:c.4651C>T NP_001305760.1:p.Arg1551Cys missense NM_001318832.2:c.5215C>T NP_001305761.1:p.Arg1739Cys missense NM_001363528.2:c.5185C>T NP_001350457.1:p.Arg1729Cys missense NM_001370404.1:c.5251C>T NP_001357333.1:p.Arg1751Cys missense NM_001370405.1:c.5242C>T NP_001357334.1:p.Arg1748Cys missense NM_021055.3:c.5254C>T NP_066399.2:p.Arg1752Cys missense NC_000016.10:g.2088569C>T NC_000016.9:g.2138570C>T NG_005895.1:g.44264C>T NG_008617.1:g.54652G>A LRG_487:g.44264C>T LRG_487t1:c.5383C>T - Protein change
- R1795C, R1728C, R1752C, R1692C, R1729C, R1772C, R1551C, R1739C, R1680C, R1748C, R1751C
- Other names
- p.R1795C:CGC>TGC
- Canonical SPDI
- NC_000016.10:2088568:C:T
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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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0.00080 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00078
1000 Genomes Project 0.00080
Exome Aggregation Consortium (ExAC) 0.00122
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00131
Trans-Omics for Precision Medicine (TOPMed) 0.00143
The Genome Aggregation Database (gnomAD), exomes 0.00148
The Genome Aggregation Database (gnomAD) 0.00156
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 | ||
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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 |
10621 | 10796 |
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. |
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Benign/Likely benign (11) |
criteria provided, multiple submitters, no conflicts
|
Jan 1, 2024 | RCV000034665.41 | |
Benign (2) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000054862.15 | |
not provided (1) |
no classification provided
|
- | RCV000055245.10 | |
Uncertain significance (1) |
no assertion criteria provided
|
Jun 1, 2014 | RCV000148917.11 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 15, 2022 | RCV000163344.13 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Dec 27, 2021 | RCV000178483.25 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000989443.16 | |
Benign (1) |
criteria provided, single submitter
|
Mar 27, 2019 | RCV001197128.10 |
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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Likely benign
(Jan 24, 2017)
|
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: SCV000540604.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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: This variant is classified in HGMD as DM and seen in 7 papers, including in patients who inherited the mutation from unaffected parents. This variant is present in gnomAD with a Max MAF of 0.36% of Ashkenazi Jews (36/10110 chrs and homozygous in 1 Latino). High for tuberous sclerosis incidence of 1/25000-1/11300. The variant is classified with 1 star in ClinVar as VUS by 3 submitters (CSER_CC_NCGL, University of Chicago, and Ambry), Likely benign by 3 submitters (Emory, Invitae, Biesecker), and Benign by GeneDx. (less)
Method: Genome/Exome Filtration
|
|
Benign
(Dec 04, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000844592.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
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Likely benign
(Dec 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000249208.2
First in ClinVar: Oct 05, 2015 Last updated: Jan 29, 2022 |
|
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Benign
(Dec 04, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221472.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
|
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Likely benign
(Jan 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213878.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely 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)
|
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139769.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
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Benign
(Mar 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Lymphangiomyomatosis
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367764.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
|
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Likely benign
(May 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884758.3
First in ClinVar: Mar 08, 2017 Last updated: Jan 26, 2021 |
|
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Benign
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002040296.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000261971.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 14, 2024 |
|
|
Likely Benign
(Nov 30, 2016)
|
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: SCV000511761.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Converted during submission to Likely benign.
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Likely benign
(Jul 15, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000230568.5
First in ClinVar: Jun 28, 2015 Last updated: Oct 05, 2015 |
Number of individuals with the variant: 2
Sex: mixed
|
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Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000395686.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Nov 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000243618.10
First in ClinVar: Aug 07, 2015 Last updated: Oct 05, 2015 |
Comment:
This variant is associated with the following publications: (PMID: 22703879, 24055113, 25637381, 21309039, 11208653, 27884173, 27153395, 26332594)
|
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Benign
(Oct 27, 2020)
|
criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002534067.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
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Likely benign
(Mar 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360948.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
|
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Likely benign
(Jan 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001150727.19
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
TSC2: BS1
Number of individuals with the variant: 24
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
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: SCV001924673.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
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Uncertain significance
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Tuberous sclerosis and lymphangiomyomatosis
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190670.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
|
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001797538.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
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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: SCV001807722.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
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Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743981.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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probably not pathogenic
(Jul 13, 2012)
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no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043548.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Likely benign.
Number of individuals with the variant: 2
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)
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965340.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
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not provided
(-)
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no classification provided
Method: curation
|
TSC
LAM
Affected status: yes
Allele origin:
germline
|
Tuberous sclerosis database (TSC2)
Accession: SCV000083464.2
First in ClinVar: Sep 16, 2013 Last updated: Sep 16, 2013 |
|
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not provided
(-)
|
no classification provided
Method: curation
|
TSC
Affected status: yes
Allele origin:
germline
|
Tuberous sclerosis database (TSC2)
Accession: SCV000067067.3
First in ClinVar: May 03, 2013 Last updated: Sep 16, 2013 |
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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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Sex-Based Analysis of De Novo Variants in Neurodevelopmental Disorders. | Turner TN | American journal of human genetics | 2019 | PMID: 31785789 |
Revisiting the morbid genome of Mendelian disorders. | Abouelhoda M | Genome biology | 2016 | PMID: 27884173 |
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 |
Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
Actionable exomic incidental findings in 6503 participants: challenges of variant classification. | Amendola LM | Genome research | 2015 | PMID: 25637381 |
Actionable, pathogenic incidental findings in 1,000 participants' exomes. | Dorschner MO | American journal of human genetics | 2013 | PMID: 24055113 |
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 |
TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios. | Langkau N | European journal of pediatrics | 2002 | PMID: 12111193 |
Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis. | Sato T | Journal of human genetics | 2002 | PMID: 11829138 |
The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. | Strizheva GD | American journal of respiratory and critical care medicine | 2001 | PMID: 11208653 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TSC2 | - | - | - | - |
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Text-mined citations for rs45517423 ...
HelpRecord last updated May 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.