Introduction: Brugada syndrome is a disorder in which the heart rhythm and normal heart rate are disturbed. If left untreated, irregular heartbeats can cause syncope, seizure, shortness of breath, or sudden death, which usually occur at rest or sleep times. Based on the studies conducted, the prevalence of the disease has been reported in Southeast Asia and Europe. Due to the lack of accurate statistics of this disease in Iran, the present study was conducted to investigate the genetic of this disease using a molecular method in Iranian families. Materials and Methods: Nine families with Brugada syndrome were selected. Genomic DNA was extracted from whole blood sample and the quality and quantity of the extracted DNA were evaluated by using bynanodrop and electrophoresis. Also, the entire coding region and intron-exon boundaries of CACNA1C was amplified by the PCR technique in each proband. Subsequently, PCR products were subjected to direct sequencing. Co-segregation analysis of the identified mutation was conducted in the family members. Results and Discussion: Direct PCR sequencing revealed a single nucleotide change: g.2659186 G>A The results showed a shift from base G to base A in the Missense type of G490R variant and caused a change in amino acid. The G490R mutation was co-segregated in affected family members but not in those that were unaffected Conclusion: In general, the results showed that the G490R type of CACNA1C might play a major role in the pathogenesis of BRs. Although our findings support CACNA1C as a plausible candidate gene responsible for Brugada syndrome, other chromosomal loci and genes could be involved.. Taken together, our results suggest that p. G490R could have possible pathogenic influences on Brugada syndrome.