Submissions for variant NM_000548.5(TSC2):c.1110G>A (p.Gln370=)

gnomAD frequency: 0.00823  dbSNP: rs1800742

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118697	SCV000153112	benign	not specified	2013-11-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000118697	SCV000169102	benign	not specified	2012-03-20	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000118697	SCV000205283	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Gln370Gln in exon 11 of TSC2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.5% (125/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800742).
Ambry Genetics	RCV000163259	SCV000213787	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: 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.
Invitae	RCV000204769	SCV000262195	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000118697	SCV000305138	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042396	SCV000395571	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 Inc	RCV000204769	SCV000677532	benign	Tuberous sclerosis 2	2017-05-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586320	SCV000697458	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The c.1110G>A (p.Gln370=) 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 0.01 predominantly in individuals of European descent (0.016; 1083/65734) including 12 homozygous spread through 4 out of 6 populations. The variant of interest has been reported as polymorphism via publications and cited as 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586320	SCV001159144	benign	not provided	2023-11-13	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000204769	SCV002041300	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000118697	SCV002774063	benign	not specified	2021-11-16	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000204769	SCV004016104	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000204769	SCV004360855	benign	Tuberous sclerosis 2	2019-03-29	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042396	SCV000066186	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000118697	SCV001808843	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000118697	SCV001919396	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118697	SCV001972441	benign	not specified		no assertion criteria provided	clinical testing