Submissions for variant NM_000548.5(TSC2):c.1318G>A (p.Gly440Ser)

gnomAD frequency: 0.00111  dbSNP: rs45484298

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000122204	SCV000153113	likely benign	not specified	2014-12-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163424	SCV000213969	likely benign	Hereditary cancer-predisposing syndrome	2018-08-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
GeneDx	RCV000034643	SCV000243540	likely benign	not provided	2021-07-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15798777, 10205261, 17304050, 24728327, 22703879)
Invitae	RCV000227708	SCV000285236	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891471	SCV000305143	benign	TSC2-related condition	2020-12-01	criteria provided, single submitter	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).
Eurofins Ntd Llc (ga)	RCV000122204	SCV000340586	likely benign	not specified	2016-03-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054863	SCV000395576	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000227708	SCV000493815	uncertain significance	Tuberous sclerosis 2	2016-01-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034643	SCV000605464	likely benign	not provided	2023-08-24	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034643	SCV000610912	likely benign	not provided	2017-06-20	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000227708	SCV002041151	likely benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034643	SCV002497854	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TSC2: BS1
Sema4, Sema4	RCV000163424	SCV002532768	likely benign	Hereditary cancer-predisposing syndrome	2021-04-21	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000227708	SCV004189643	benign	Tuberous sclerosis 2	2023-10-09	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000227708	SCV004360861	benign	Tuberous sclerosis 2	2022-08-18	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034643	SCV000043526	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2)	RCV000054863	SCV000067257	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000122204	SCV000086425	not provided	not specified	2013-09-19	no assertion provided	reference population
Department of Genetics, Reproduction and Fetal Medicine., Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville.	RCV000201296	SCV000222732	uncertain significance	Hirschsprung disease, susceptibility to, 1	2015-04-01	flagged submission	research
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000227708	SCV000296948	uncertain significance	Tuberous sclerosis 2	2015-10-30	flagged submission	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034643	SCV001744727	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034643	SCV001808982	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000034643	SCV001917005	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000122204	SCV001975366	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000034643	SCV002036928	likely benign	not provided		no assertion criteria provided	clinical testing