Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690331 | SCV000818013 | uncertain significance | Tuberous sclerosis 2 | 2018-05-17 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants 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). However, exon 32 has been shown to undergo alternative splicing and results in transcripts lacking exon 32 in many adult human tissues (PMID: 7558029, 8519695). This sequence change affects an acceptor splice site in intron 31 of the TSC2 gene. This variant may disrupt RNA splicing, however the extent to which this occurs is not known. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC2-related disease. 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. |