Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000806792 | SCV000946810 | uncertain significance | Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E | 2023-08-31 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 135 of the OPTN protein (p.Glu135Lys). This variant is present in population databases (rs140599944, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 651429). 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 | RCV002352386 | SCV002619787 | uncertain significance | Inborn genetic diseases | 2020-06-18 | criteria provided, single submitter | clinical testing | The p.E135K variant (also known as c.403G>A), located in coding exon 3 of the OPTN gene, results from a G to A substitution at nucleotide position 403. The glutamic acid at codon 135 is replaced by lysine, an amino acid with similar properties. This amino acid position is not 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. |