ClinVar Miner

Submissions for variant NM_130837.3(OPA1):c.740G>A (p.Arg247His)

gnomAD frequency: 0.00002  dbSNP: rs138350727
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657875 SCV000779636 uncertain significance not provided 2018-05-11 criteria provided, single submitter clinical testing The R247H variant in the OPA1 gene has been reported previously in an individual with optic neuropathy. Studies in fibroblasts from this affected individual demonstrated increased susceptibility to apoptosis, abnormal mitochondrial network filamentation, and altered OPA1 protein profile; however, the significance of these findings is unknown (Cornille et al., 2008). The R247H variant is observed in 9/277,158 (0.0032%) alleles in large population cohorts (Lek et al., 2016). The R247H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret R247H as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000657875 SCV002302456 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with OPA1-related conditions (PMID: 18360822). The OPA1 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_130837.2, and corresponds to NM_015560.2:c.625-5459G>A in the primary transcript. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 247 of the OPA1 protein (p.Arg247His). This variant is present in population databases (rs138350727, gnomAD 0.01%). ClinVar contains an entry for this variant (Variation ID: 65755). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneReviews RCV000055988 SCV000087042 not provided Autosomal dominant optic atrophy classic form no assertion provided literature only

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