ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2098-1G>A (rs45517212)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229589 SCV000285277 pathogenic Tuberous sclerosis 2 2019-12-19 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the TSC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with TSC2-related disease (PMID: 11520734, 17304050). ClinVar contains an entry for this variant (Variation ID: 49730). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000482722 SCV000567134 pathogenic not provided 2015-07-14 criteria provided, single submitter clinical testing The c.2098-1 G>A splice site variant in the TSC2 gene has been previously reportedmultiple times in association with tuberous sclerosis complex (TSC) (Dabora et al., 2001;Au et al., 2007; TSC2 LOVD). This variant destroys the canonical splice acceptor site in intron 19, and is expected to cause abnormal gene splicing. Therefore, we interpret the c.2098-1 variant in TSC2 as pathogenic.
Tuberous sclerosis database (TSC2) RCV000042995 SCV000066793 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000042995 SCV000083434 not provided Tuberous sclerosis syndrome no assertion provided curation

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