Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668665 | SCV000793300 | likely pathogenic | Neuronal ceroid lipofuscinosis 2 | 2017-08-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003767965 | SCV004686376 | likely pathogenic | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 553258). Disruption of this splice site has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 19201763). This sequence change affects a donor splice site in intron 1 of the TPP1 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 TPP1 are known to be pathogenic (PMID: 10330339). |