ClinVar Miner

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

dbSNP: rs1057523242
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001698247 SCV000531214 likely pathogenic not provided 2019-03-20 criteria provided, single submitter clinical testing Identified in an individual with tuberous sclerosis complex and inherited from an unaffected parent (Lee et al., 2014); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 25498131)
Invitae RCV000817980 SCV000958568 pathogenic Tuberous sclerosis 2 2019-01-09 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed to be de novo in an individual affected with TSC2-related disease (Invitae). This variant has also been reported in an individual affected with tuberous sclerosis complex whom inherited the variant from an unaffected parent in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 388832). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 4 of the TSC2 gene. It does not directly change the encoded amino acid sequence of the TSC2 protein, but it affects a nucleotide within the consensus splice site of the intron.
Genome-Nilou Lab RCV000817980 SCV002040912 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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