Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000674890 | SCV000800300 | likely pathogenic | Neuronal ceroid lipofuscinosis 8 | 2018-06-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002544675 | SCV003440633 | pathogenic | Neuronal ceroid lipofuscinosis | 2022-12-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CLN8 protein in which other variant(s) (p.Trp263Cys) have been determined to be pathogenic (PMID: 15024724; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 558594). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 28116333). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs746397087, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln255*) in the CLN8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32 amino acid(s) of the CLN8 protein. |