Submissions for variant NM_000368.5(TSC1):c.1936A>G (p.Met646Val)

gnomAD frequency: 0.00016  dbSNP: rs145741748

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130315	SCV000185165	likely benign	Hereditary cancer-predisposing syndrome	2019-04-11	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.
GeneDx	RCV001579757	SCV000243504	benign	not provided	2020-12-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000464079	SCV000478219	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.
Illumina Laboratory Services, Illumina	RCV000295067	SCV000478220	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464079	SCV000562485	benign	Tuberous sclerosis 1	2025-02-01	criteria provided, single submitter	clinical testing
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV000464079	SCV001430711	likely benign	Tuberous sclerosis 1	2020-07-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000464079	SCV002040406	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001579757	SCV002048752	likely benign	not provided	2024-02-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130315	SCV002530945	benign	Hereditary cancer-predisposing syndrome	2021-01-11	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002492502	SCV002798816	likely benign	Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II	2021-07-12	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000464079	SCV004016081	likely benign	Tuberous sclerosis 1	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000464079	SCV005404669	likely benign	Tuberous sclerosis 1	2024-08-12	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
CeGaT Center for Human Genetics Tuebingen	RCV001579757	SCV005431725	likely benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	TSC1: BP4, BS1
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV002492502	SCV006053208	likely benign	Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II	2023-08-28	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000189851	SCV001742787	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579757	SCV001808424	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001579757	SCV001923098	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000189851	SCV001965040	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935217	SCV004764372	likely benign	TSC1-related disorder	2019-11-13	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).