ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4569+2T>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Myriad Genetics, Inc. RCV003452623 SCV004189833 likely pathogenic Tuberous sclerosis 2 2023-09-19 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003452623 SCV004538943 pathogenic Tuberous sclerosis 2 2025-01-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 35 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: 29476190, 31525612). ClinVar contains an entry for this variant (Variation ID: 2674428). 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.

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