Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001235198 | SCV001407874 | pathogenic | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant results in the deletion of part of exon 4 (c.376_380+6del) 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). This variant has been observed in individuals with neuronal ceroid lipofuscinosis (PMID: 10330339). For these reasons, this variant has been classified as 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: 961500). This variant is also known as 3081-3091del. |