Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001057571 | SCV001222070 | uncertain significance | Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E | 2023-09-10 | criteria provided, single submitter | clinical testing | 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. This sequence change falls in intron 12 of the OPTN gene. It does not directly change the encoded amino acid sequence of the OPTN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373981784, gnomAD 0.01%). 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: 852864). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. |
Gene |
RCV001760007 | SCV001990198 | uncertain significance | not provided | 2019-07-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
Dept. |
RCV001843559 | SCV002103166 | uncertain significance | Amyotrophic lateral sclerosis | 2022-01-01 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002400329 | SCV002706672 | uncertain significance | Inborn genetic diseases | 2021-12-06 | criteria provided, single submitter | clinical testing | The c.1533-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 12 in the OPTN gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |