Submissions for variant NM_000368.5(TSC1):c.532G>A (p.Val178Ile)

gnomAD frequency: 0.00014  dbSNP: rs118203395

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164135	SCV000214750	likely benign	Hereditary cancer-predisposing syndrome	2018-04-27	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228124	SCV000284730	benign	Tuberous sclerosis 1	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000724965	SCV000484491	uncertain significance	not provided	2015-06-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000724965	SCV000518098	benign	not provided	2021-04-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 10363127, 9863590, 24728327, 30842500)
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000228124	SCV000928337	uncertain significance	Tuberous sclerosis 1	2018-02-27	criteria provided, single submitter	clinical testing	PP3
CeGaT Center for Human Genetics Tuebingen	RCV000724965	SCV001155803	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TSC1: BP5
Illumina Laboratory Services, Illumina	RCV001165738	SCV001327970	benign	Isolated focal cortical dysplasia type II	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.
Illumina Laboratory Services, Illumina	RCV000228124	SCV001327971	likely benign	Tuberous sclerosis 1	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000724965	SCV002009238	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000228124	SCV002040156	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164135	SCV002531466	benign	Hereditary cancer-predisposing syndrome	2020-11-18	criteria provided, single submitter	curation
Tuberous sclerosis database (TSC1)	RCV000042305	SCV000066094	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
ITMI	RCV000122198	SCV000086417	not provided	not specified	2013-09-19	no assertion provided	reference population
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000724965	SCV001977718	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000724965	SCV001978797	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964895	SCV004784343	likely benign	TSC1-related disorder	2019-04-23	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).