NM_021098.2(CACNA1H):c.[2318G>A;2362C>T] AND Epilepsy, childhood absence 6

Significance: risk factor
ClinVar: RCV000002823

Variant: NM_021098.2(CACNA1H):c.[2318G>A;2362C>T]

Type: Haplotype
Allele: NM_021098.3(CACNA1H):c.2318G>A (p.Gly773Asp) 17743
Type: single nucleotide variant
Location: Chr16: 1254325 - assembly GRCh37
Chr16: 1204325 - assembly GRCh38
References: dbSNP: 267606697
OMIM: 607904.0004
UniProtKB: O95180#VAR_045946
Allele: NM_021098.3(CACNA1H):c.2362C>T (p.Arg788Cys) 38427
Type: single nucleotide variant
Location: Chr16: 1254369 - assembly GRCh37
Chr16: 1204369 - assembly GRCh38
References: dbSNP: 3751664
OMIM: 607904.0004
UniProtKB: O95180#VAR_045948
HGMD: CM076042


Disease: Epilepsy, childhood absence 6


    In 2 unrelated Chinese Han patients with childhood absence epilepsy (611942), Chen et al. (2003) identified a heterozygous 2397G-A transition in exon 10 of the CACNA1H gene, resulting in a gly773-to-asp (G773D) substitution in the linker region between domains I and II. In these same 2 patients and a third unrelated patient, Vitko et al. (2005) found that all 3 had the G773D variant on the same allele as a common arg788-to-cys (R788C) polymorphism. In vitro functional expression studies by Vitko et al. (2005) demonstrated that both the G773D and the R788C variants independently altered the voltage dependence of channel activation, and together resulted in an even stronger propensity for enhanced neuronal firing. Vitko et al. (2005) noted that the findings supported the idea that variants in the CACNA1H gene are susceptibility alleles that contribute to the development of polygenic disorders such as idiopathic generalized epilepsy.
PMID:12891677, PMID:15888660