Submissions for variant NM_000548.5(TSC2):c.3889G>A (p.Ala1297Thr) (rs45517319)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129666	SCV000184464	benign	Hereditary cancer-predisposing syndrome	2014-12-09	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	RCV000122229	SCV000229650	benign	not specified	2015-01-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000122229	SCV000243587	likely benign	not specified	2017-09-27	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.
Invitae	RCV000231518	SCV000285372	benign	Tuberous sclerosis 2	2019-12-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia	RCV000231518	SCV000296950	benign	Tuberous sclerosis 2	2015-11-10	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000122229	SCV000305209	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000054864	SCV000395636	benign	Tuberous sclerosis syndrome	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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000122229	SCV000605469	benign	not specified	2019-05-09	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000231518	SCV000677543	benign	Tuberous sclerosis 2	2017-05-24	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000034653	SCV000697465	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.3889G>A (p.Ala1297Thr) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 193/33944 control chromosomes at a frequency of 0.0056858, which is approximately 83 times the estimated maximal expected allele frequency of a pathogenic TSC2 variant (0.0000688), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Center for Human Genetics, Inc,Center for Human Genetics, Inc	RCV000231518	SCV000782408	uncertain significance	Tuberous sclerosis 2	2016-11-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000231518	SCV001440892	likely benign	Tuberous sclerosis 2	2019-01-01	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034653	SCV000043536	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2)	RCV000054864	SCV000066967	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000122229	SCV000086451	not provided	not specified	2013-09-19	no assertion provided	reference population