Submissions for variant NM_000744.7(CHRNA4):c.1060C>T (p.Arg354Cys)

gnomAD frequency: 0.00001  dbSNP: rs758534439

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000475005	SCV000553233	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy	2023-07-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 354 of the CHRNA4 protein (p.Arg354Cys). This variant is present in population databases (rs758534439, gnomAD 0.006%). 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: 411846). 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000997799	SCV001153513	uncertain significance	not provided	2017-10-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003144275	SCV003832063	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 1	2021-07-22	criteria provided, single submitter	clinical testing