Submissions for variant NM_000368.5(TSC1):c.2646C>T (p.Ala882=)

gnomAD frequency: 0.00269  dbSNP: rs118203720

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125633	SCV000169093	benign	not specified	2013-03-01	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	RCV000163300	SCV000213828	likely benign	Hereditary cancer-predisposing syndrome	2014-08-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000125633	SCV000249202	likely benign	not specified	2021-12-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000125633	SCV000269916	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Ala882Ala in exon 21 of TSC1: 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 0.5% (41/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs118203720).
Invitae	RCV000231700	SCV000284705	benign	Tuberous sclerosis 1	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000125633	SCV000303864	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000125633	SCV000337485	benign	not specified	2015-11-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000384965	SCV000478193	benign	Isolated focal cortical dysplasia type II	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.
Illumina Laboratory Services, Illumina	RCV000231700	SCV000478194	benign	Tuberous sclerosis 1	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528699	SCV001159691	benign	not provided	2023-10-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000231700	SCV002040042	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163300	SCV002528891	benign	Hereditary cancer-predisposing syndrome	2020-07-02	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001528699	SCV002546109	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TSC1: BP4, BP7, BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000125633	SCV004122243	benign	not specified	2023-10-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001528699	SCV004221391	benign	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000231700	SCV004360807	benign	Tuberous sclerosis 1	2022-08-17	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC1)	RCV000042235	SCV000066021	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC1)	RCV000054945	SCV000083161	not provided	Malignant tumor of urinary bladder		no assertion provided	curation
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528699	SCV001740887	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001528699	SCV001809172	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001528699	SCV001920588	likely benign	not provided		no assertion criteria provided	clinical testing