Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001219343 | SCV001391278 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 233 of the WWOX protein (p.His233Asn). This variant is present in population databases (rs757863128, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with WWOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 948143). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. |
Gene |
RCV001751418 | SCV002006935 | uncertain significance | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |