Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658343 | SCV000780115 | uncertain significance | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | The M114T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M114T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The M114T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000696611 | SCV000825177 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 114 of the WWOX protein (p.Met114Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 546463). 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 WWOX protein function. 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. |
| Fulgent Genetics, |
RCV000764077 | SCV000895038 | uncertain significance | Malignant tumor of esophagus; Autosomal recessive spinocerebellar ataxia 12; Developmental and epileptic encephalopathy, 28 | 2018-10-31 | criteria provided, single submitter | clinical testing |