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NM_000368.4(TSC1):c.1460C>G (p.Ser487Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(2);Likely benign(5);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
10 (Most recent: Sep 24, 2021)
Last evaluated:
Dec 7, 2020
Accession:
VCV000041690.12
Variation ID:
41690
Description:
single nucleotide variant
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NM_000368.4(TSC1):c.1460C>G (p.Ser487Cys)

Allele ID
50129
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q34.13
Genomic location
9: 132906118 (GRCh38) GRCh38 UCSC
9: 135781505 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000009.11:g.135781505G>C
NC_000009.12:g.132906118G>C
NG_012386.1:g.43516C>G
... more HGVS
Protein change
S487C, S486C, S436C, S366C
Other names
p.S487C:TCT>TGT
Canonical SPDI
NC_000009.12:132906117:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (C)

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00032
The Genome Aggregation Database (gnomAD), exomes 0.00045
The Genome Aggregation Database (gnomAD) 0.00013
Exome Aggregation Consortium (ExAC) 0.00045
Links
Tuberous sclerosis database (TSC1): TSC1_00343
dbSNP: rs118203532
ClinGen: CA004868
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign/Likely benign 3 criteria provided, multiple submitters, no conflicts Oct 1, 2020 RCV000034602.8
Benign/Likely benign 2 criteria provided, multiple submitters, no conflicts Dec 7, 2020 RCV001085737.3
Likely benign 1 criteria provided, single submitter Jun 16, 2016 RCV000189811.7
Likely benign 1 criteria provided, single submitter Apr 27, 2017 RCV000319085.2
Likely benign 1 criteria provided, single submitter Aug 8, 2018 RCV000568490.1
Uncertain significance 1 criteria provided, single submitter Mar 21, 2016 RCV000761004.1
not provided 1 no assertion provided - RCV000054845.4
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TSC1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2790 2834

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Benign
(Dec 07, 2020)
criteria provided, single submitter
Method: clinical testing
Tuberous sclerosis 1
Allele origin: germline
Invitae
Accession: SCV000284676.7
Submitted: (Jan 07, 2021)
Evidence details
Uncertain significance
(Mar 21, 2016)
criteria provided, single submitter
Method: clinical testing
Primitive neuroectodermal tumor
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV000890919.1
Submitted: (Dec 04, 2018)
Evidence details
Likely benign
(Aug 08, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000664629.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Insufficient or conflicting evidence;Other strong data supporting benign classification;Subpopulation frequency in support of benign classification
Likely benign
(Jun 16, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000342691.4
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Likely benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Tuberous sclerosis 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000478231.3
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (2)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Focal cortical dysplasia type II
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000478232.3
Submitted: (Feb 20, 2020)
Evidence details
Publications
PubMed (1)
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Benign
(Apr 18, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000243461.12
Submitted: (Sep 24, 2021)
Evidence details
Comment:
This variant is associated with the following publications: (PMID: 21309039, 27153395, 16554133, 23514105, 22703879, 31054281)
Likely benign
(Oct 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001502115.3
Submitted: (Jul 04, 2021)
Evidence details
variant of unknown significance
(Jul 13, 2012)
no assertion criteria provided
Method: research
not provided
Allele origin: germline
Biesecker Lab/Clinical Genomics Section,National Institutes of Health
Study: ClinSeq
Accession: SCV000043515.1
Submitted: (Jul 15, 2012)
Evidence details
Publications
PubMed (1)
Comment:
Converted during submission to Uncertain significance.
not provided
(-)
no assertion provided
Method: curation
TSC
Allele origin: germline
Tuberous sclerosis database (TSC1)
Accession: SCV000065815.3
Submitted: (Aug 09, 2013)
Evidence details

Functional evidence

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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 this variant

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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
The impact of reporting incidental findings from exome and whole-genome sequencing: predicted frequencies based on modeling. Ding LE Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25077650
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
Mutational analysis of TSC1 and TSC2 in Korean patients with tuberous sclerosis complex. Choi JE Brain & development 2006 PMID: 16554133
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TSC1 - - - -

Text-mined citations for rs118203532...

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These 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 07, 2021