Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002651772 | SCV003525685 | pathogenic | not provided | 2022-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.1099C>T (p.Arg367X). This premature translational stop signal has been observed in individual(s) with autosomal dominant optical atrophy (PMID: 29111013). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg312*) 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). |
| Center for Genomic Medicine, |
RCV003988067 | SCV004804713 | pathogenic | Autosomal dominant optic atrophy classic form | 2024-03-17 | criteria provided, single submitter | research | |
| Institute of Medical Genetics and Applied Genomics, |
RCV003988067 | SCV005038797 | pathogenic | Autosomal dominant optic atrophy classic form | 2024-04-30 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003988067 | SCV005400225 | pathogenic | Autosomal dominant optic atrophy classic form | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with OPA1-related conditions (OMIM). (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 (PMID: 17306754). (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). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have previously been reported as pathogenic (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in at least five unrelated individuals with autosomal dominant optic atrophy or optic atrophy plus syndrome (ClinVar, PMID: 16331355, 36661516, 25796301, 35936615, 29111013). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Prevention |
RCV004738699 | SCV005344203 | pathogenic | OPA1-related disorder | 2024-03-12 | no assertion criteria provided | clinical testing | The OPA1 c.1099C>T variant is predicted to result in premature protein termination (p.Arg367*). This variant has been reported in the heterozygous state in multiple affected individuals from a family with optic atrophy as well as in additional unrelated individuals with optic atrophy (described as R312X, Cardaioli et al. 2006. PubMed ID: 16331355; Galvez-Ruiz et al. 2013. PubMed ID: 24051421; patient OFT-00677, Arruti et al. 2023. PubMedID: 36661516). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic. |