ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5068+1G>A

dbSNP: rs45445199
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001222160 SCV001394248 pathogenic Tuberous sclerosis 2 2019-04-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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). 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. Disruption of this splice site has been observed in individuals affected with tuberous sclerosis complex (PMID: 19419980, 25782670). ClinVar contains an entry for this variant (Variation ID: 50026). This variant is not present in population databases (ExAC no frequency). 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.
GeneDx RCV001795037 SCV002032615 pathogenic not provided 2021-06-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27535533, 19419980)
Genome-Nilou Lab RCV001222160 SCV002041015 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043292 SCV000067098 not provided Tuberous sclerosis syndrome no assertion provided curation

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