ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.336+1G>A

dbSNP: rs45517102
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476030 SCV000544583 pathogenic Tuberous sclerosis 2 2024-01-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the TSC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with tuberous sclerosis complex (TSC2) (PMID: 12015165, 21520333). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 50064). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003332095 SCV004039863 pathogenic not provided 2023-03-29 criteria provided, single submitter clinical testing Identified as a somatic variant in a patient with seizures and focal cortical dysplasia type II, although additional clinical information was not provided (Macdonald-Laurs et al., 2023); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 21533266, 21520333, 35403742, 12015165, 17304050, 36527426)
Tuberous sclerosis database (TSC2) RCV000043330 SCV000067136 not provided Tuberous sclerosis syndrome no assertion provided curation

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