Submissions for variant NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys)

gnomAD frequency: 0.00156  dbSNP: rs45517423

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163344	SCV000213878	likely benign	Hereditary cancer-predisposing syndrome	2019-03-12	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.
Eurofins Ntd Llc (ga)	RCV000178483	SCV000230568	likely benign	not specified	2014-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000034665	SCV000243618	benign	not provided	2018-11-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22703879, 24055113, 25637381, 21309039, 11208653, 27884173, 27153395, 26332594)
Genetic Services Laboratory, University of Chicago	RCV000178483	SCV000249208	likely benign	not specified	2021-12-27	criteria provided, single submitter	clinical testing
Invitae	RCV000989443	SCV000261971	benign	Tuberous sclerosis 2	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054862	SCV000395686	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	RCV000034665	SCV000511761	likely benign	not provided	2016-11-30	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000178483	SCV000540604	likely benign	not specified	2017-01-24	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is classified in HGMD as DM and seen in 7 papers, including in patients who inherited the mutation from unaffected parents. This variant is present in gnomAD with a Max MAF of 0.36% of Ashkenazi Jews (36/10110 chrs and homozygous in 1 Latino). High for tuberous sclerosis incidence of 1/25000-1/11300. The variant is classified with 1 star in ClinVar as VUS by 3 submitters (CSER_CC_NCGL, University of Chicago, and Ambry), Likely benign by 3 submitters (Emory, Invitae, Biesecker), and Benign by GeneDx.
Athena Diagnostics Inc	RCV000034665	SCV000844592	benign	not provided	2017-12-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034665	SCV000884758	likely benign	not provided	2020-05-05	criteria provided, single submitter	clinical testing
Mendelics	RCV000989443	SCV001139769	benign	Tuberous sclerosis 2	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034665	SCV001150727	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TSC2: BS1
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197128	SCV001367764	benign	Lymphangiomyomatosis	2019-03-27	criteria provided, single submitter	clinical testing	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
Genome-Nilou Lab	RCV000989443	SCV002040296	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163344	SCV002534067	benign	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034665	SCV004221472	benign	not provided	2017-12-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000989443	SCV004360948	likely benign	Tuberous sclerosis 2	2018-03-05	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034665	SCV000043548	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2)	RCV000054862	SCV000067067	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055245	SCV000083464	not provided	Lymphangiomyomatosis; Tuberous sclerosis syndrome		no assertion provided	curation
CSER _CC_NCGL, University of Washington	RCV000148917	SCV000190670	uncertain significance	Tuberous sclerosis and lymphangiomyomatosis	2014-06-01	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034665	SCV001743981	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000034665	SCV001797538	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000034665	SCV001807722	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000034665	SCV001924673	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000178483	SCV001965340	benign	not specified		no assertion criteria provided	clinical testing