ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1335A>G (p.Glu445=) (rs7862221)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118690 SCV000169083 benign not specified 2013-10-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000118690 SCV000200858 benign not specified 2013-02-21 criteria provided, single submitter clinical testing Glu445Glu in exon 14 of TSC1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 21.9% (965/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs7862221).
Ambry Genetics RCV000162953 SCV000213440 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000118690 SCV000226017 benign not specified 2014-07-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000118690 SCV000303846 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000287833 SCV000478237 benign Focal cortical dysplasia type II 2018-01-12 criteria provided, single submitter clinical testing 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.
Illumina Clinical Services Laboratory,Illumina RCV000576803 SCV000478238 benign Tuberous sclerosis 1 2018-01-12 criteria provided, single submitter clinical testing 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.
Athena Diagnostics Inc RCV000576803 SCV000677526 benign Tuberous sclerosis 1 2017-04-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586425 SCV000696599 benign not provided 2016-05-26 criteria provided, single submitter clinical testing Variant summary: The TSC1 c.1335A>G (p.Glu445Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change 2 nucleotides from the exon14-intron13 boundary. One in silico tool predicts a polymorphism outcome for this variant. 5/5 Alamut algorithms predict no significant change to the cononical splice acceptor site, while 2/5 predict a strengthening of a cryptic splice acceptor site. This variant was found in 16480/120190 control chromosomes (1225 homozygotes) at a frequency of 0.1371162, which is approximately 5485 times the estimated maximal expected allele frequency of a pathogenic TSC1 variant (0.000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as benign, and it has been reported in the literature as a normal population variant (PMID: 18538015). Taken together and based on the high allele frequency in the general population, this variant is classified as Benign.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute,Kanazawa Medical University RCV000576803 SCV001430713 benign Tuberous sclerosis 1 2020-07-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285925 SCV001472438 benign none provided 2020-08-27 criteria provided, single submitter clinical testing
Invitae RCV000576803 SCV001722509 benign Tuberous sclerosis 1 2020-12-08 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC1) RCV000042015 SCV000065797 not provided Tuberous sclerosis syndrome no assertion provided curation
Genetic Services Laboratory, University of Chicago RCV000118690 SCV000153105 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

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