Submissions for variant NM_021098.3(CACNA1H):c.3445G>T (p.Gly1149Cys)

dbSNP: rs753696656

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001883318	SCV002143704	uncertain significance	Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV	2021-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with cysteine at codon 1149 of the CACNA1H protein (p.Gly1149Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. 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 CACNA1H 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.