ClinVar Miner

Submissions for variant NM_015560.2(OPA1):c.2797G>A (p.Val933Ile) (rs375733283)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489553 SCV000577786 likely pathogenic not provided 2015-05-15 criteria provided, single submitter clinical testing The V933I variant in the OPA1 gene has been published in two affected individuals in the same family with dominant optic atrophy (Barboni et al., 2010). Missense variants in nearby residues (R932C, L939P) also have been reported in the Human Gene Mutation Database in association with optic atrophy (Stenson et al., 2014), supporting the functional importance of this region of the protein. The V933I variant was not observed at any significant frequency 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. This substitution also occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the V933I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. We interpret the V933I variant as a strong candidate for a disease-causing variant however, the possibility V933I may be a rare benign variant cannot be excluded
Illumina Clinical Services Laboratory,Illumina RCV001146349 SCV001307090 uncertain significance Autosomal dominant optic atrophy classic form 2017-09-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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