Submissions for variant NM_000368.5(TSC1):c.1438+6G>A

gnomAD frequency: 0.00009  dbSNP: rs118203530

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083129	SCV000284675	benign	Tuberous sclerosis 1	2024-01-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000385329	SCV000478233	likely 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 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	RCV001083129	SCV000478234	uncertain significance	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, 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.
GeneDx	RCV000227291	SCV000514996	likely benign	not provided	2020-12-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000227291	SCV001155798	likely benign	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001083129	SCV002040107	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002256017	SCV002530905	likely benign	Hereditary cancer-predisposing syndrome	2021-03-04	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001727548	SCV004221380	benign	not specified	2022-08-30	criteria provided, single submitter	clinical testing	The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. Computational tools yielded predictions that this variant is unlikely to have an effect on normal RNA splicing. This nucleotide position exhibits low evolutionary conservation.
All of Us Research Program, National Institutes of Health	RCV000042029	SCV004824181	likely benign	Tuberous sclerosis syndrome	2024-01-11	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC1)	RCV000042029	SCV000065811	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000227291	SCV001806865	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000227291	SCV001917023	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727548	SCV001973191	benign	not specified		no assertion criteria provided	clinical testing