ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.1588C>A (p.Gln530Lys)

gnomAD frequency: 0.00003  dbSNP: rs759605171
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001864914 SCV002126813 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2024-04-11 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 530 of the OPTN protein (p.Gln530Lys). This variant is present in population databases (rs759605171, gnomAD 0.009%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 29525178). ClinVar contains an entry for this variant (Variation ID: 1360254). 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 not expected to disrupt OPTN protein function with a negative 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 RCV002397798 SCV002705683 uncertain significance Inborn genetic diseases 2020-03-21 criteria provided, single submitter clinical testing The p.Q530K variant (also known as c.1588C>A), located in coding exon 12 of the OPTN gene, results from a C to A substitution at nucleotide position 1588. The glutamine at codon 530 is replaced by lysine, an amino acid with similar properties. This alteration was noted in a single individual with a clinical diagnosis of amyotrophic lateral sclerosis; however, it is unknown if this alteration was detected in a heterozygous, compound heterozygous, or homozygous state (Lamp M et al. Neurobiol. Aging, 2018 06;66:179.e5-179.e16). This amino acid position is well conserved in available 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.
PreventionGenetics, part of Exact Sciences RCV004536383 SCV004119474 uncertain significance OPTN-related disorder 2023-03-14 criteria provided, single submitter clinical testing The OPTN c.1588C>A variant is predicted to result in the amino acid substitution p.Gln530Lys. This variant was reported in an individual with sporadic amyotrophic lateral sclerosis who also carried an in-frame deletion in the HNRNPA1 gene (Lamp et al 2018. PubMed ID: 29525178). This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-13175557-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.