Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040398 | SCV001203970 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 391 of the WWOX protein (p.Glu391Gly). This variant is present in population databases (rs369959670, gnomAD 0.05%). 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: 838781). 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 WWOX 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. |
| Gene |
RCV001585939 | SCV001821157 | uncertain significance | not provided | 2024-01-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004678900 | SCV005175220 | uncertain significance | Inborn genetic diseases | 2024-06-07 | criteria provided, single submitter | clinical testing | The c.1172A>G (p.E391G) alteration is located in exon 9 (coding exon 9) of the WWOX gene. This alteration results from a A to G substitution at nucleotide position 1172, causing the glutamic acid (E) at amino acid position 391 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782630 | SCV005394810 | uncertain significance | not specified | 2024-09-23 | criteria provided, single submitter | clinical testing | Variant summary: WWOX c.1172A>G (p.Glu391Gly) results in a non-conservative amino acid change located in the WWOX, classical (c)-like SDR domain (IPR042732) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 249538 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in WWOX causing Autosomal Recessive Early Infantile Epileptic Encephalopathy, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1172A>G in individuals affected with Early Infantile Epileptic Encephalopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 838781). Based on the evidence outlined above, the variant was classified as uncertain significance. |