Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494434 | SCV000582333 | pathogenic | not provided | 2015-09-02 | criteria provided, single submitter | clinical testing | The Q263X nonsense variant in the TPP1 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. A nonsense variant in a nearby residue (Q264X) as well as other nonsense variants in TPP1 have been reported in the Human Gene Mutation Database in association with neuronal ceroid lipofuscinosis (NCL) (Stenson et al., 2014). Although the Q263X varianthas not been reported previously to our knowledge, it is interpreted to be pathogenic. |
| Invitae | RCV000494434 | SCV001578036 | pathogenic | not provided | 2022-07-23 | criteria provided, single submitter | clinical testing | 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: 429701). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln263*) in the TPP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPP1 are known to be pathogenic (PMID: 10330339). |