Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000478916 | SCV000569460 | uncertain significance | not provided | 2016-02-23 | criteria provided, single submitter | clinical testing | The E373K variant in the CHRNA4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E373K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E373K 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. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to)] the protein structure/function. We interpret E373K as a variant of uncertain significance. |
Invitae | RCV001041676 | SCV001205302 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2019-04-18 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CHRNA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 420576). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 373 of the CHRNA4 protein (p.Glu373Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |