Submissions for variant NM_000548.5(TSC2):c.482-3C>T

gnomAD frequency: 0.12927  dbSNP: rs1800720

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118710	SCV000200860	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	482-3C>T in intron 5 of TSC2: This variant is not expected to have clinical sign ificance because it has been identified in 19.1% (838/4396) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs1800720).
Ambry Genetics	RCV000163048	SCV000213539	benign	Hereditary cancer-predisposing syndrome	2014-11-21	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
PreventionGenetics, part of Exact Sciences	RCV000118710	SCV000305231	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000043224	SCV000395559	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.
Athena Diagnostics	RCV000576589	SCV000677551	benign	Tuberous sclerosis 2	2017-04-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589095	SCV000697471	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: c.482-3C>T in TSC2 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing pattern, 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 0.087 (10574/121392 chrs tested), predominantly in individuals of African descent (0.2; 2098/10406 chrs tested) including numerous homozygous occurrences. The observed frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.00006 suggesting that it is a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but cited as Benign/ Likely Benign by multiple reputable databases/clinical laboratory. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589095	SCV001156849	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Invitae	RCV000576589	SCV001730598	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000589095	SCV001905370	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000576589	SCV002041229	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000576589	SCV004016091	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000576589	SCV004360847	benign	Tuberous sclerosis 2	2018-03-05	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000043224	SCV000067025	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055133	SCV000083351	not provided	Neoplasm of brain		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055419	SCV000083640	not provided	Lymphangiomyomatosis; Tuberous sclerosis syndrome		no assertion provided	curation
Genetic Services Laboratory, University of Chicago	RCV000118710	SCV000153125	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.
Clinical Genetics, Academic Medical Center	RCV000118710	SCV001922097	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000118710	SCV001930505	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118710	SCV001969058	benign	not specified		no assertion criteria provided	clinical testing