Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000685645 | SCV000813132 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 618 of the CHRNA4 protein (p.Phe618Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 565952). 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 not expected to disrupt CHRNA4 protein function with a negative 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. |
| Ambry Genetics | RCV003380672 | SCV004090156 | uncertain significance | Inborn genetic diseases | 2023-09-14 | criteria provided, single submitter | clinical testing | The c.1854C>G (p.F618L) alteration is located in exon 6 (coding exon 6) of the CHRNA4 gene. This alteration results from a C to G substitution at nucleotide position 1854, causing the phenylalanine (F) at amino acid position 618 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |