ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.1396G>T (p.Ala466Ser)

gnomAD frequency: 0.00034  dbSNP: rs144466778
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001972901 SCV002252361 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2024-06-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 466 of the OPTN protein (p.Ala466Ser). This variant is present in population databases (rs144466778, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1468951). 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 OPTN protein function with a positive predictive value of 80%. 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.
Ambry Genetics RCV002388961 SCV002700183 uncertain significance Inborn genetic diseases 2023-01-23 criteria provided, single submitter clinical testing Unlikely to be causative of OPTN-related amyotrophic lateral sclerosis (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004734373 SCV005355514 uncertain significance OPTN-related disorder 2024-09-26 no assertion criteria provided clinical testing The OPTN c.1396G>T variant is predicted to result in the amino acid substitution p.Ala466Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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