ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.287G>A (p.Arg96His)

gnomAD frequency: 0.00002  dbSNP: rs184561087
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001244376 SCV001417595 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 96 of the OPTN protein (p.Arg96His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs184561087, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002436959 SCV002751254 uncertain significance Inborn genetic diseases 2022-08-22 criteria provided, single submitter clinical testing The p.R96H variant (also known as c.287G>A), located in coding exon 2 of the OPTN gene, results from a G to A substitution at nucleotide position 287. The arginine at codon 96 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.