Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797052 | SCV000936591 | likely pathogenic | Tuberous sclerosis 1 | 2018-10-23 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 4 of the TSC1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TSC1-related disease. ClinVar contains an entry for this variant (Variation ID: 64762). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). A different variant affecting this nucleotide (c.211-1G>A, also known as 432-1G>A) has been determined to be pathogenic (PMID: 10227394). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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. |
| Tuberous sclerosis database |
RCV000054944 | SCV000083160 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |