Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000992464 | SCV001144801 | likely pathogenic | not provided | 2018-12-27 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality (0/281614 chr). |
Labcorp Genetics |
RCV002549795 | SCV003256150 | likely pathogenic | Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E | 2024-10-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 9 of the OPTN 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 OPTN are known to be pathogenic (PMID: 20428114). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 805103). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Gene |
RCV000992464 | SCV004028419 | likely pathogenic | not provided | 2023-08-14 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |