Submissions for variant NM_000548.5(TSC2):c.5321G>C (p.Ser1774Thr)

gnomAD frequency: 0.00948  dbSNP: rs9209

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163420	SCV000213963	benign	Hereditary cancer-predisposing syndrome	2015-04-06	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.
Eurofins Ntd Llc (ga)	RCV000118714	SCV000230569	benign	not specified	2015-04-02	criteria provided, single submitter	clinical testing
Invitae	RCV001084407	SCV000261874	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034662	SCV000280897	likely benign	not provided	2015-08-19	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences	RCV000118714	SCV000305252	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054870	SCV000395683	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000034662	SCV000697478	benign	not provided	2017-06-16	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.5321G>C (p.Ser1774Thr) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 359/119808 control chromosomes (6 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.033497 (342/10210). This frequency is about 487 times the estimated maximal expected allele frequency of a pathogenic TSC2 variant (0.0000688), strong evidence that this is a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034662	SCV001157617	benign	not provided	2020-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000034662	SCV001837394	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24728327, 17304050, 22903760)
Genome-Nilou Lab	RCV001084407	SCV002039950	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163420	SCV002534052	benign	Hereditary cancer-predisposing syndrome	2020-09-10	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002482951	SCV002800432	likely benign	Polycystic kidney disease, adult type	2021-11-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034662	SCV004010434	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BS1, BS2
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001084407	SCV004016155	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034662	SCV000043545	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
Tuberous sclerosis database (TSC2)	RCV000054870	SCV000066988	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000118714	SCV000086465	not provided	not specified	2013-09-19	no assertion provided	reference population
Genetic Services Laboratory, University of Chicago	RCV000118714	SCV000153129	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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000118714	SCV001809195	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118714	SCV001966702	benign	not specified		no assertion criteria provided	clinical testing