ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.849-1G>A (rs45506396)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439973 SCV000516737 pathogenic not provided 2015-04-14 criteria provided, single submitter clinical testing The c.849-1 G>A splice site variant in the TSC2 gene has been reported previously in association withtuberous sclerosis (Choy et al., 1999). Thisvariant destroys the canonical splice acceptor site in intron 9,and is expected to cause abnormal gene splicing. Therefore, we interpret this variant to be pathogenic.
Invitae RCV001039254 SCV001202777 likely pathogenic Tuberous sclerosis 2 2019-04-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 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 an individual affected with tuberous sclerosis complex (PMID: 10735580). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042648 SCV000066443 not provided Tuberous sclerosis syndrome no assertion provided curation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.