Submissions for variant NM_000548.5(TSC2):c.1281C>A (p.Ile427=)

gnomAD frequency: 0.00202  dbSNP: rs45478892

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000174491	SCV000169107	benign	not specified	2013-10-23	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	RCV000163377	SCV000213917	likely benign	Hereditary cancer-predisposing syndrome	2014-11-02	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)	RCV000174491	SCV000225800	likely benign	not specified	2014-12-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205713	SCV000261678	benign	Tuberous sclerosis 2	2025-02-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000174491	SCV000305141	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042948	SCV000395574	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000429983	SCV000511452	benign	not provided	2016-07-13	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000174491	SCV000597591	likely benign	not specified	2015-08-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000205713	SCV000677534	benign	Tuberous sclerosis 2	2017-05-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000429983	SCV000697459	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The c.1281C>A (p.Ile427=) in TSC2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0022 (201/93004 chrs tested), predominantly in individuals of European descent (0.0032; 161/50172). This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000068). The variant of interest has been cited as Benign/Likely Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
CeGaT Center for Human Genetics Tuebingen	RCV000429983	SCV001150687	likely benign	not provided	2024-12-01	criteria provided, single submitter	clinical testing	TSC2: BP4, BP7
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000429983	SCV001470957	benign	not provided	2024-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000205713	SCV002041145	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163377	SCV002532763	likely benign	Hereditary cancer-predisposing syndrome	2021-03-12	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000174491	SCV002774064	benign	not specified	2021-12-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496678	SCV002804437	likely benign	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-04-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000205713	SCV004360859	benign	Tuberous sclerosis 2	2022-09-20	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000042948	SCV004819245	benign	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000205713	SCV005881410	benign	Tuberous sclerosis 2	2025-02-01	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042948	SCV000066745	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055284	SCV000083504	not provided	Lymphangiomyomatosis		no assertion provided	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000429983	SCV001808645	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000429983	SCV001922603	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000174491	SCV001975931	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000429983	SCV001979779	likely benign	not provided		no assertion criteria provided	clinical testing