ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2221-2A>G (rs45502196)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694650 SCV000823107 pathogenic Tuberous sclerosis 2 2018-06-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 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 to be de novo in an individual affected with tuberous sclerosis complex (PMID: 29196670). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 49815). 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.
Tuberous sclerosis database (TSC2) RCV000043081 SCV000066880 not provided Tuberous sclerosis syndrome no assertion provided curation

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