Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000081749 | SCV000226147 | pathogenic | not provided | 2013-05-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000081749 | SCV000252017 | pathogenic | not provided | 2016-08-05 | criteria provided, single submitter | clinical testing | The R445H missense variant in the OPA1 gene has been reported previously in a patient with optic atrophy and hearing loss and in a patient with optic atrophy and motor instability due to vestibular dysfunction (Huang et al., 2009; Mizutari et al., 2010). The R445H variant was associated with reduced function in vivo when expressed in OPA1-null mouse embryonic fibroblasts, and in vitro studies showed that R445H is associated with reduced levels of the OPA1 protein's GTP hydrolysis activity (Ban et al., 2010). The R445H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the R445H variant is a conservative amino acid substitution, this substitution occurs at a position that is well conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R445H as a disease-causing variant |
OMIM | RCV000005396 | SCV000025576 | pathogenic | Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy | 2008-11-25 | no assertion criteria provided | literature only | |
Gene |
RCV000005396 | SCV000041283 | pathologic | Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy | 2010-07-20 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Wellcome Centre for Mitochondrial Research, |
RCV000508953 | SCV000575920 | pathogenic | Mitochondrial diseases | 2017-04-07 | no assertion criteria provided | clinical testing |