Submissions for variant NM_000368.5(TSC1):c.3123C>G (p.Ser1041Arg)

gnomAD frequency: 0.00006  dbSNP: rs753374839

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705062	SCV000243477	likely benign	not provided	2022-03-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000225953	SCV000284715	benign	Tuberous sclerosis 1	2025-01-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000341814	SCV000478181	likely 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 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	RCV000225953	SCV000478182	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome-Nilou Lab	RCV000225953	SCV002040012	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257479	SCV002531421	benign	Hereditary cancer-predisposing syndrome	2020-12-24	criteria provided, single submitter	curation
Ambry Genetics	RCV002257479	SCV002607503	likely benign	Hereditary cancer-predisposing syndrome	2021-12-17	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.
All of Us Research Program, National Institutes of Health	RCV004804807	SCV005426901	likely benign	Tuberous sclerosis syndrome	2024-09-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003416119	SCV004115170	likely benign	TSC1-related disorder	2024-04-10	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).