ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.2974del (p.Arg992fs) (rs1554813210)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000642020 SCV000763673 uncertain significance Tuberous sclerosis 1 2017-09-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TSC1 gene (p.Arg992Glyfs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 173 amino acids of the TSC1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC1-related disease. Although functional studies have not been done for this particular variant, experimental studies have shown that deletion of exon 23 (the last 172 amino acids) of the TSC1 protein decreases the protein stability and its interaction with TSC2, but has no effect on the downstream S6K signaling (PMID: 24714658). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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