Background Mutations in the SCN1A gene have been associated with various epileptic phenotypes. This study aimed (i) to examine the SCN1A-mutations in North-Indian population. (ii) to evaluate Glial fibrillary acidic protein (GFAP), Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and interleukin 1β (IL-1β) levels in epileptic patients and correlate it with clinical characteristics. (iii) to establish the correlation between GFAP, UCH-L1 and IL-1β levels with SCN1Ac.3199G>A polymorphism. Methods We collected clinical and genetic information from randomly selected genetic generalized epilepsy (GGE) patients and performed SCN1A mutation screening using NGS. Variants were validated using PCR-RFLP assay and further correlated with GFAP, UCH-L1 and IL-1β levels using ELISA and seizure severity assessed using Chalfont severity scale in the population (n=95; 60 case and 35 control). Results SCN1A targeted exome sequencing identified 67 novel mutations including a common missense mutation (SCN1Ac.3199G>A/p.Ala1067→Thr) which were detected in 40% of patient population among the cohort. Also, this polymorphism was more prevalent among children than the adult and was found to be correlated with IL-1β level in patients of North-Indian origin. Additionally, elevated level of GFAP was found to be associated with seizure severity in GGE population. Conclusions The study unveils 67 novel mutations in SCN1A gene and also establishes a direct correlation between a disease specific polymorphism rs2298771 with serum IL-1β level in adult population. Also, the study shows the paediatric predominance of rs2298771 mutation. The findings of the study will have theragnostic impact on the management of epilepsy.