ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5068+2T>C (rs397515152)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521796 SCV000617955 pathogenic not provided 2015-12-23 criteria provided, single submitter clinical testing The c.5068+2 T>C splice site variant in the TSC2 gene destroys the canonical splice donor site in intron 2. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Many other splice variants have been reported in the Human Gene Mutation Database in association with tuberous sclerosis (Stenson et al., 2014).
Invitae RCV000704780 SCV000833744 pathogenic Tuberous sclerosis 2 2018-05-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 39 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 (Invitae). ClinVar contains an entry for this variant (Variation ID: 449636). 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.
Mendelics RCV000704780 SCV001139766 pathogenic Tuberous sclerosis 2 2019-05-28 criteria provided, single submitter clinical testing

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