ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2870dup (p.Leu957fs)

dbSNP: rs1567490680
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003512070 SCV004248013 uncertain significance Tuberous sclerosis 2 2023-11-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu957Phefs*3) in the TSC2 gene. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). However, tissue-specific alternative splicing of TSC2 gene results in a functional isoform lacking in-frame exon 26 (also known as exon 25, PMID: 26703369). For this reason the clinical significance of loss of function variants in exon 26 is currently uncertain. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with chronic kidney disease (PMID: 30586318). ClinVar contains an entry for this variant (Variation ID: 562247). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Gharavi Laboratory, Columbia University RCV000681682 SCV000809129 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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