ClinVar Miner

Submissions for variant NM_130837.3(OPA1):c.1511C>G (p.Thr504Arg)

dbSNP: rs1577244261
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987381 SCV001136665 pathogenic Autosomal dominant optic atrophy classic form 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002549677 SCV003525385 pathogenic not provided 2022-02-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 449 of the OPA1 protein (p.Thr449Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with OPA1-related conditions (PMID: 19319978; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 802041). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OPA1 protein function. This variant disrupts the p.Thr449 amino acid residue in OPA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23387428). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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