Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001771602 | SCV002003547 | uncertain significance | not provided | 2020-01-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; 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. |
| Labcorp Genetics |
RCV003120677 | SCV003788202 | uncertain significance | 3-Methylglutaconic aciduria type 3; Optic atrophy 3 | 2022-07-07 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 142 of the OPA3 protein (p.Ala142Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OPA3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1314371). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |