ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.682C>T (p.His228Tyr)

gnomAD frequency: 0.00001  dbSNP: rs775448931
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001202904 SCV001374039 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2022-08-10 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 934500). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. This variant is present in population databases (rs775448931, gnomAD 0.004%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 228 of the OPTN protein (p.His228Tyr).
Athena Diagnostics Inc RCV001289044 SCV001476585 uncertain significance not provided 2020-03-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002365912 SCV002665244 uncertain significance Inborn genetic diseases 2020-11-17 criteria provided, single submitter clinical testing The p.H228Y variant (also known as c.682C>T), located in coding exon 5 of the OPTN gene, results from a C to T substitution at nucleotide position 682. The histidine at codon 228 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant amyotrophic lateral sclerosis (ALS); however, its contribution to the development of autosomal recessive ALS is uncertain.

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