Submissions for variant NM_000548.5(TSC2):c.4662+1G>A

dbSNP: rs45514095

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415345	SCV000492780	pathogenic	Intellectual disability, severe; Infantile spasms	2015-10-20	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198320	SCV001369208	pathogenic	Lymphangiomyomatosis	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003511998	SCV004296678	pathogenic	Tuberous sclerosis 2	2024-04-05	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 36 of the TSC2 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 TSC2 are known to be pathogenic (PMID: 10205261, 17304050). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with tuberous sclerosis complex (PMID: 27859028). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 50031). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV003511998	SCV005368076	pathogenic	Tuberous sclerosis 2	2024-04-08	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PS4_MOD,PM2_SUP
Tuberous sclerosis database (TSC2)	RCV000043297	SCV000067103	not provided	Tuberous sclerosis syndrome		no assertion provided	curation