Submissions for variant NM_000368.5(TSC1):c.364-2A>G

dbSNP: rs1846685279

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001199393	SCV003241187	pathogenic	Tuberous sclerosis 1	2021-12-16	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 5 of the TSC1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 932153). Disruption of this splice site has been observed in individuals with clinical features of tuberous sclerosis complex (PMID: 9863590; Invitae).
Myriad Genetics, Inc.	RCV001199393	SCV004189830	likely pathogenic	Tuberous sclerosis 1	2023-09-07	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University	RCV001199393	SCV001370510	pathogenic	Tuberous sclerosis 1	2020-06-09	no assertion criteria provided	clinical testing