ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.941A>T (p.Gln314Leu)

gnomAD frequency: 0.00007  dbSNP: rs142812715
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Genomic and Experimental Medicine, University of Edinburgh RCV000492386 SCV000323225 pathogenic Motor neuron disease 2016-08-31 criteria provided, single submitter case-control
Labcorp Genetics (formerly Invitae), Labcorp RCV000557693 SCV000632382 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2024-10-03 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 314 of the OPTN protein (p.Gln314Leu). This variant is present in population databases (rs142812715, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of OPTN-related conditions (PMID: 21613650, 23138764, 25382069, 28089114, 31000212, 32028661, 33770234, 36133075, 36570531). ClinVar contains an entry for this variant (Variation ID: 266060). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on OPTN 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.
CeGaT Center for Human Genetics Tuebingen RCV002059063 SCV002497021 uncertain significance not provided 2022-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002374436 SCV002687142 uncertain significance Inborn genetic diseases 2022-06-02 criteria provided, single submitter clinical testing The p.Q314L variant (also known as c.941A>T), located in coding exon 7 of the OPTN gene, results from an A to T substitution at nucleotide position 941. The glutamine at codon 314 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant amyotrophic lateral sclerosis; however, its contribution to the development of autosomal recessive amyotrophic lateral sclerosis is uncertain.
Athena Diagnostics RCV002059063 SCV004229821 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with amyotrophic lateral sclerosis. Computational tools predict that this variant is damaging.

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