ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.275A>T (p.Glu92Val) (rs137853994)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130758 SCV000185649 benign Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification;Subpopulation frequency in support of benign classification
GeneDx RCV001703939 SCV000243626 benign not provided 2019-03-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21407264, 23514105, 22558107, 21624971, 24728327, 28873162, 29801666)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000122217 SCV000270956 likely benign not specified 2020-07-01 criteria provided, single submitter clinical testing The c.275A>T variant in TSC2 has been reported in individuals with Tuberous Sclerosis Complex (Dunlop 2011 PMID: 21407264, Bullich 2018 PMID: 29801666); however, it has also been identified in 0.17% (189/109664) of Finnish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 50116). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. This variant is classified as Likely Benign due to its frequency in the general population. ACMG/AMP Criteria applied: BS1, BP4.
Invitae RCV000989412 SCV000285313 benign Tuberous sclerosis 2 2020-12-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000122217 SCV000305186 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000043383 SCV000395556 benign Tuberous sclerosis syndrome 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000122217 SCV000703518 benign not specified 2016-12-27 criteria provided, single submitter clinical testing
Mendelics RCV000989412 SCV001139734 likely benign Tuberous sclerosis 2 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000122217 SCV001338115 likely benign not specified 2020-01-27 criteria provided, single submitter clinical testing Variant summary: TSC2 c.275A>T (p.Glu92Val) results in a non-conservative amino acid change located in the N-terminal domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 213250 control chromosomes (gnomAD). The observed variant frequency is approximately 14.6- fold the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is benign. c.275A>T has been reported in the literature in individuals affected with Tuberous Sclerosis Complex (examples-Dunlop_2011, Bullich_2018) and in at least one unaffected family member (Dunlop_2011). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Dunlop_2011). Seven ClinVar submitters (evaluation after 2014) classified the variant as benign (n=2)/likely benign (n=5). Based on the evidence outlined above, the variant was classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001289631 SCV001477594 likely benign none provided 2020-04-09 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043383 SCV000067189 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000122217 SCV000086438 not provided not specified 2013-09-19 no assertion provided reference population

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.