Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521072 | SCV000619944 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | clinical testing | The V375F variant in the RBFOX1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V375F variant is observed in 1/24012 (0.005%) alleles from individuals of African background and 6/276578 total alleles in the ExAC dataset (Lek et al., 2016). The V375F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret V375F as a variant of uncertain significance. |
Labcorp Genetics |
RCV001061679 | SCV001226429 | uncertain significance | Idiopathic generalized epilepsy | 2022-10-24 | 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 451270). This variant has not been reported in the literature in individuals affected with RBFOX1-related conditions. This variant is present in population databases (rs138704494, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 375 of the RBFOX1 protein (p.Val375Phe). |