Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001245132 | SCV001418401 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2022-11-01 | 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. This variant disrupts the p.Ser284 amino acid residue in CHRNA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10563623, 10939581, 12887446, 14623738, 22118295). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CHRNA4 function (PMID: 36292983). 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: 969721). This missense change has been observed in individual(s) with autosomal dominant nocturnal frontal lobe epilepsy (PMID: 36292983; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 284 of the CHRNA4 protein (p.Ser284Trp). |