Submissions for variant NM_000548.5(TSC2):c.5359G>A (p.Gly1787Ser)

gnomAD frequency: 0.00264  dbSNP: rs45517419

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000122242	SCV000169166	benign	not specified	2013-03-03	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	RCV000130722	SCV000185609	benign	Hereditary cancer-predisposing syndrome	2015-01-09	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
CSER _CC_NCGL, University of Washington	RCV000054855	SCV000212204	benign	Tuberous sclerosis syndrome	2015-03-11	criteria provided, single submitter	research
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202756	SCV000257720	benign	Tuberous sclerosis 2	2015-03-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000202756	SCV000285462	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000122242	SCV000337047	likely benign	not specified	2015-11-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054855	SCV000395685	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034663	SCV000609598	benign	not provided	2017-05-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000202756	SCV000677557	benign	Tuberous sclerosis 2	2017-05-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000034663	SCV000697479	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.5359G>A (p.Gly1787Ser) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 303/119148 control chromosomes at a frequency of 0.0025431, which is approximately 37 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034663	SCV002011319	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000202756	SCV002040291	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034663	SCV002048124	benign	not provided	2023-09-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000122242	SCV002070031	likely benign	not specified	2021-07-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130722	SCV002534061	benign	Hereditary cancer-predisposing syndrome	2020-08-12	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000034663	SCV002545722	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BS2
Color Diagnostics, LLC DBA Color Health	RCV000202756	SCV004360947	likely benign	Tuberous sclerosis 2	2018-03-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000054855	SCV004817517	likely benign	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034663	SCV000043546	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2)	RCV000054855	SCV000066425	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000122242	SCV000086466	not provided	not specified	2013-09-19	no assertion provided	reference population
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034663	SCV001809584	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534724	SCV004733404	benign	TSC2-related disorder	2019-08-01	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).