Submissions for variant NM_000548.5(TSC2):c.1443+5G>C

dbSNP: rs1057521562

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579379	SCV000681119	likely pathogenic	not provided	2019-09-10	criteria provided, single submitter	clinical testing	Reported as apparently de novo in a patient in a well-curated database but additional evidence is not available (TSC2 LOVD); Intronic +5 splice site variant predicted to result in aberrant splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29476190)
Invitae	RCV000644207	SCV000765898	likely pathogenic	Tuberous sclerosis 2	2017-12-27	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported to be de novo in an individual affected with tuberous sclerosis in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 14 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.