ClinVar Miner

Submissions for variant NM_015560.2(OPA1):c.1334G>A (p.Arg445His) (rs80356529)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000081749 SCV000226147 pathogenic not provided 2013-05-29 criteria provided, single submitter clinical testing
GeneDx 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
GeneReviews 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,Newcastle University RCV000508953 SCV000575920 pathogenic Mitochondrial diseases 2017-04-07 no assertion criteria provided clinical testing

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