Submissions for variant NM_000368.5(TSC1):c.2626-4del

dbSNP: rs5901000

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000313026	SCV000478203	benign	Isolated focal cortical dysplasia type II	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000042234	SCV000478204	benign	Tuberous sclerosis syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586305	SCV000696602	benign	not provided	2016-05-26	criteria provided, single submitter	clinical testing	Variant summary: The TSC1 c.2626-4delT variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant effect on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 22671/80186 (1 homozygote, 1/3, frequency: 0.2827302), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TSC1 variant of 1/40000(0.000025), suggesting this variant is likely a benign polymorphism. Therefore, the variant of interest has been classified as Benign.
GeneDx	RCV000586305	SCV000730260	benign	not provided	2018-06-12	criteria provided, single submitter	clinical testing
Invitae	RCV001514617	SCV001722507	benign	Tuberous sclerosis 1	2024-01-20	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001514617	SCV002040371	benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV001514617	SCV002503767	benign	Tuberous sclerosis 1	2022-04-22	criteria provided, single submitter	clinical testing	Population allele frequency is 19% (rs118203716, 22,767/119,574 alleles in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria is met: BA1.
Sema4, Sema4	RCV002256019	SCV002528884	benign	Hereditary cancer-predisposing syndrome	2019-12-09	criteria provided, single submitter	curation
Ambry Genetics	RCV002256019	SCV002744645	benign	Hereditary cancer-predisposing syndrome	2020-07-06	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Color Diagnostics, LLC DBA Color Health	RCV001514617	SCV004360810	benign	Tuberous sclerosis 1	2022-08-17	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC1)	RCV000042234	SCV000066020	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795035	SCV002035580	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001795035	SCV002038181	benign	not specified		no assertion criteria provided	clinical testing