ClinVar Miner

Submissions for variant NM_015560.2(OPA1):c.1146A>G (p.Ile382Met) (rs143319805)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081747 SCV000113682 uncertain significance not provided 2014-02-15 criteria provided, single submitter clinical testing
GeneDx RCV000081747 SCV000251994 likely pathogenic not provided 2018-10-11 criteria provided, single submitter clinical testing The I382M variant in the OPA1 gene was originally reported in a single patient in association with autosomal dominant optic atrophy I (Schimpf et al., 2008). However, later this variant was shown to not be pathogenic alone, even when in the homozygous state (Bonifert et al., 2014). The I382M variant was reported as a phenotypic modifier when present in trans with an OPA1 pathogenic variant, leading to a phenotype of optic atrophy plus ataxia, ophthalmoplegia, peripheral neuropathy, muscle atrophy, ptosis, and spasticity (Schaaf et al., 2011; Bonifert et al., 2014). The I382M variant is observed in 28/30,780 alleles (0.09%) from individuals of South Asian background, and 166/276,896 global alleles (0.06%), in large population cohorts (Lek et al., 2016). Although the I382M variant is a conservative amino acid substitution, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret I382M as a likely pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000316085 SCV000442626 likely benign Optic Atrophy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000081747 SCV000802494 uncertain significance not provided 2017-08-18 no assertion criteria provided clinical testing
OMIM RCV000043607 SCV000071625 pathogenic Dominant hereditary optic atrophy 2011-08-01 no assertion criteria provided literature only
OMIM RCV000210748 SCV000266835 pathogenic Abortive cerebellar ataxia 2011-08-01 no assertion criteria provided literature only
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000677258 SCV000681433 uncertain significance Optic nerve hypoplasia criteria provided, single submitter research

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