ClinVar Miner

Submissions for variant NM_130837.3(OPA1):c.1148A>G (p.Lys383Arg)

dbSNP: rs398124303
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000081775 SCV000233132 pathogenic not provided 2015-10-22 criteria provided, single submitter clinical testing
GeneDx RCV000081775 SCV000251992 pathogenic not provided 2021-05-27 criteria provided, single submitter clinical testing RT-PCR analysis demonstrates that c.983 A>G modifies the consensus splice donor site in intron 9 resulting in in-frame skipping of exon 9 (Baris et al., 2003); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 14961560, 22857269, 26385429, 25699009, 16418602, 23384603, 30581410, 16735988, 20301426, 22042570, 27535533, 25525159)
Athena Diagnostics RCV000081775 SCV000614395 pathogenic not provided 2023-09-07 criteria provided, single submitter clinical testing This variant has been identified in multiple unrelated individuals with optic atrophy. Experimental evidence suggests this variant results in abnormal RNA splicing and an in-frame deletion of 38 amino acids from the protein (PMID: 14961560). This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). The variant is located in a region that is considered important for protein function and/or structure. Computational tools predict that this variant is damaging.
Invitae RCV000081775 SCV002240849 pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 328 of the OPA1 protein (p.Lys328Arg). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with dominant optic atrophy (PMID: 14961560, 22857269). ClinVar contains an entry for this variant (Variation ID: 95733). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in skipping of exon 9, but is expected to preserve the integrity of the reading-frame (PMID: 14961560). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000180653 SCV000256797 not provided Autosomal dominant optic atrophy classic form no assertion provided literature only

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