Submissions for variant NM_000548.5(TSC2):c.4285G>T (p.Ala1429Ser)

gnomAD frequency: 0.00306  dbSNP: rs45474795

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000122234	SCV000169149	benign	not specified	2013-04-11	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	RCV000163285	SCV000213813	benign	Hereditary cancer-predisposing syndrome	2014-12-11	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.
Genetic Services Laboratory, University of Chicago	RCV000122234	SCV000249207	likely benign	not specified	2015-03-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000122234	SCV000305217	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054858	SCV000395650	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.
Invitae	RCV000468567	SCV000556595	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000468567	SCV000677547	benign	Tuberous sclerosis 2	2017-05-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034658	SCV000884754	benign	not provided	2022-08-22	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034658	SCV002011330	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000122234	SCV002014848	likely benign	not specified	2021-10-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000468567	SCV002039445	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034658	SCV002497861	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BS1
Sema4, Sema4	RCV000163285	SCV002533522	benign	Hereditary cancer-predisposing syndrome	2020-08-18	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002504868	SCV002797992	likely benign	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2021-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000468567	SCV004360918	benign	Tuberous sclerosis 2	2022-09-20	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034658	SCV000043541	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
Tuberous sclerosis database (TSC2)	RCV000054858	SCV000066566	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055296	SCV000083516	not provided	Autism spectrum disorder		no assertion provided	curation
ITMI	RCV000122234	SCV000086457	not provided	not specified	2013-09-19	no assertion provided	reference population
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000122234	SCV001807414	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000122234	SCV001923599	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000122234	SCV001969208	benign	not specified		no assertion criteria provided	clinical testing