Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001222252 | SCV001394346 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 334 of the CHRNA4 protein (p.Ser334Leu). This variant is present in population databases (rs121912262, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This missense change has been observed in at least one individual who was not affected with CHRNA4-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 98300). 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 with a positive 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. |
| Psychiatry Genetics Yale University | RCV000084590 | SCV000116726 | not provided | Tobacco use disorder | no assertion provided | not provided |