Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000275327 | SCV000330081 | pathogenic | not provided | 2018-09-20 | criteria provided, single submitter | clinical testing | The c.2640-2 A>G splice site variant in the TSC2 gene destroys the canonical splice acceptor site in intron 23. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this variant has not been previously reported to our knowledge, we interpret it to be pathogenic. |
| Labcorp Genetics |
RCV001855061 | SCV002301077 | pathogenic | Tuberous sclerosis 2 | 2025-01-15 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 23 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 (PMID: 32313033). ClinVar contains an entry for this variant (Variation ID: 280185). 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. |
| Fulgent Genetics, |
RCV002487175 | SCV002787811 | likely pathogenic | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2021-07-14 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Department, |
RCV001855061 | SCV004801880 | likely pathogenic | Tuberous sclerosis 2 | criteria provided, single submitter | clinical testing | A previously undescribed nucleotide variant creates an alteration of the canonical splice site c.2640-2A>G in the TSC2 gene. The variant was observed in heterozygous state in an individual affected with tuberous sclerosis. Loss-of-function variants are reported in patients with Tuberous sclerosis-2, 613254. The variant is not present in population database (gnomAD no frequency). 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. |