Submissions for variant NM_000548.5(TSC2):c.1276C>T (p.Leu426=)

gnomAD frequency: 0.00142  dbSNP: rs45478593

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000174492	SCV000169106	benign	not specified	2013-07-10	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	RCV000163287	SCV000213815	likely benign	Hereditary cancer-predisposing syndrome	2015-03-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Eurofins Ntd Llc (ga)	RCV000174492	SCV000225801	benign	not specified	2014-11-04	criteria provided, single submitter	clinical testing
Invitae	RCV000225838	SCV000285233	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000174492	SCV000305140	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042405	SCV000395573	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.
Athena Diagnostics	RCV000225838	SCV000677533	benign	Tuberous sclerosis 2	2017-05-30	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000174492	SCV000711362	likely benign	not specified	2017-02-06	criteria provided, single submitter	clinical testing	p.Leu426Leu in exon 13 of TSC2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.2% (125/48602) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs45478593).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001579518	SCV001472838	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000225838	SCV002041314	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000174492	SCV002069931	likely benign	not specified	2021-12-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163287	SCV002532761	benign	Hereditary cancer-predisposing syndrome	2021-01-01	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001579518	SCV004133815	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TSC2: BS1
Color Diagnostics, LLC DBA Color Health	RCV000225838	SCV004360858	benign	Tuberous sclerosis 2	2022-09-20	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000042405	SCV004819244	benign	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174492	SCV005185231	benign	not specified	2024-05-20	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042405	SCV000066195	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579518	SCV001807531	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000174492	SCV001924619	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000174492	SCV001928237	benign	not specified		no assertion criteria provided	clinical testing