Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002537913 | SCV003258724 | uncertain significance | Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E | 2024-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 516 of the OPTN protein (p.Glu516Gln). This variant is present in population databases (rs757107215, gnomAD 0.03%). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 26503823, 31838784, 32893042). ClinVar contains an entry for this variant (Variation ID: 992570). 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) 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. |
OMIM | RCV001281068 | SCV001468503 | pathogenic | Amyotrophic lateral sclerosis type 12 | 2021-01-05 | no assertion criteria provided | literature only |