Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001067398 | SCV001232458 | uncertain significance | Tuberous sclerosis 2 | 2019-12-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TSC2-related conditions. 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. 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 28 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. |
Ambry Genetics | RCV002445348 | SCV002611540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-01 | criteria provided, single submitter | clinical testing | The c.3284+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 27 in the TSC2 gene. This alteration was observed in 1 of 327 Danish individuals undergoing TSC1 and TSC2 genetic testing based on a suspicion of tuberous sclerosis complex (TSC) (Rosengren T et al. Sci Rep, 2020 06;10:9909). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |