Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000516837 | SCV000614386 | pathogenic | not provided | 2023-06-06 | criteria provided, single submitter | clinical testing | This variant is not expected to cause loss of protein expression through nonsense-mediated decay, however, similar variants in this region have been associated with disease, and therefore, this variant is also expected to contribute to disease. This variant has been identified in at least one individual with clinical features of optic atrophy. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). |
| Labcorp Genetics |
RCV000516837 | SCV002180040 | uncertain significance | not provided | 2023-03-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe952*) in the OPA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the OPA1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 447903). This variant disrupts a region of the OPA1 protein in which other variant(s) (p.His957Tyr) have been observed in individuals with OPA1-related conditions (PMID: 27974645). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |