ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3324C>T (p.Gly1108=) (rs35593170)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118694 SCV000169097 benign not specified 2013-10-14 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 RCV000163278 SCV000213806 benign Hereditary cancer-predisposing syndrome 2014-11-25 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000118694 SCV000228007 benign not specified 2014-11-22 criteria provided, single submitter clinical testing
Invitae RCV000206605 SCV000262317 benign Tuberous sclerosis 1 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000118694 SCV000303869 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000344276 SCV000478175 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 RCV000206605 SCV000478176 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.
Integrated Genetics/Laboratory Corporation of America RCV000588693 SCV000696609 benign not provided 2016-05-26 criteria provided, single submitter clinical testing Variant summary: The TSC1 c.3324C>T (p.Gly1108Gly) 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. 5/5 splice prediction tools predict the variant to result in the creation of a cyrpitc splice donor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1690/121388 control chromosomes (132 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.1302506 (1507/11570). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic TSC1 variant (0.000025), strong evidence that this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Tuberous sclerosis database (TSC1) RCV000042275 SCV000066064 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC1) RCV000054911 SCV000083126 not provided Urinary bladder cancer no assertion provided curation
Genetic Services Laboratory, University of Chicago RCV000118694 SCV000153109 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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