Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000518107 | SCV000614390 | pathogenic | not provided | 2016-10-21 | criteria provided, single submitter | clinical testing | |
| Institute of Medical Genetics and Applied Genomics, |
RCV000518107 | SCV001762094 | pathogenic | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000518107 | SCV004292243 | pathogenic | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 447904). This premature translational stop signal has been observed in individual(s) with autosomal dominant optic atrophy (PMID: 23916084, 25564500). This variant is present in population databases (rs761743852, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg235*) in the OPA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPA1 are known to be pathogenic (PMID: 11440988, 20157015, 20952381, 25012220). |
| Clinical Genetics Laboratory, |
RCV000518107 | SCV005197037 | pathogenic | not provided | 2022-07-13 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004787826 | SCV005399199 | pathogenic | Autosomal dominant optic atrophy classic form | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.2, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and this gene is associated with optic atrophy. (I) 0108 - This gene is associated with both recessive and dominant disease. Truncating variants and mutations in the C-terminal domain are associated with dominant optic atrophy. Individuals carrying missense variants are clustered within the GTPase domain, generally develop optic atrophy plus syndrome. Lastly, biallelic variants have been associated with early onset Behr syndrome (PMID: 31500643, 28494813, 25012220, 30165240). (I) 0112 - The condition associated with this gene has incomplete penetrance. A study demonstrated penetrance to be approximately 90% (PMID: 15948788). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction) (exon 7 of 29). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for both dominant and recessive conditions (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with dominant optic atrophy (ClinVar, PMID: 15948788, 24907432). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |