Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001226780 | SCV001399106 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2022-10-26 | 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. 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 expected to disrupt CHRNA4 protein function. ClinVar contains an entry for this variant (Variation ID: 954339). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This variant is present in population databases (rs773225799, gnomAD 0.009%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 314 of the CHRNA4 protein (p.Met314Val). |
| Ambry Genetics | RCV002375226 | SCV002683791 | uncertain significance | Inborn genetic diseases | 2018-11-17 | criteria provided, single submitter | clinical testing | The p.M314V variant (also known as c.940A>G), located in coding exon 5 of the CHRNA4 gene, results from an A to G substitution at nucleotide position 940. The methionine at codon 314 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |