ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1726T>C (p.Leu576=) (rs118203567)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000174844 SCV000169086 benign not specified 2013-08-02 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.
Ambry Genetics RCV000162960 SCV000213448 benign Hereditary cancer-predisposing syndrome 2014-12-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000174844 SCV000226223 benign not specified 2015-01-20 criteria provided, single submitter clinical testing
Invitae RCV001084140 SCV000261729 benign Tuberous sclerosis 1 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000174844 SCV000303851 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000297283 SCV000478229 benign Focal cortical dysplasia type II 2018-01-13 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 RCV001084140 SCV000478230 benign Tuberous sclerosis 1 2018-01-13 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.
Integrated Genetics/Laboratory Corporation of America RCV000587200 SCV000696600 benign not provided 2016-05-26 criteria provided, single submitter clinical testing Variant summary: The TSC1 c.1726T>C (p.Leu576Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant, and 5/5 Alamut algorithms predict no significant change to normal splicing. This variant was found in 458/121316 control chromosomes (16 homozygotes) at a frequency of 0.0037753, which is approximately 151 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/reputable databases classified this variant as benign. Taken together and based on the synonymous nature of this variant and the high allele frequency in the general population, this variant is classified as Benign.
Tuberous sclerosis database (TSC1) RCV000042069 SCV000065853 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC1) RCV000055008 SCV000083226 not provided Urinary bladder cancer no assertion provided curation

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