ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.403G>T (p.Glu135Ter)

dbSNP: rs140599944
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
Illumina Laboratory Services, Illumina RCV000778274 SCV000914448 uncertain significance Amyotrophic lateral sclerosis type 12 2018-12-18 criteria provided, single submitter clinical testing The OPTN c.403G>T (p.Glu135Ter) variant is a stop-gained variant predicted to result in premature termination of the protein product. The p.Glu135Ter variant has been reported in one study in which it is found in a homozygous state in one patient with amyotrophic lateral sclerosis (Müller et al. 2018). Control data are unavailable for this variant, which is reported at a frequency of 0.000081 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the potential impact of stop-gained variants and the limited evidence from the literature, the p.Glu135Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive amyotrophic lateral sclerosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869132 SCV002214900 pathogenic Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2022-10-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631627). This premature translational stop signal has been observed in individual(s) with autosomal recessive amyotrophic lateral sclerosis (PMID: 29650794). This variant is present in population databases (rs140599944, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Glu135*) in the OPTN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPTN are known to be pathogenic (PMID: 20428114).
Laboratory for Molecular Genetic Diagnostic of Neurological Diseases, University of Belgrade, School of Medicine RCV000778274 SCV001805843 pathogenic Amyotrophic lateral sclerosis type 12 2021-03-01 no assertion criteria provided clinical testing

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.