# Decoding _Scn2a_ Variants: Bridging Genetics and Phenotypes in Autism Spectrum Disorder
## 3 Results
### Genotypic Data  
The analysis of genetic mutations associated with _SCN2A_-related disorders reveals a diverse spectrum of variant types, each contributing differently to clinical presentation (Tables 3 and 4). Among the studies reviewed, missense mutations were the most frequently observed, with a total of 58 instances. [PERSON] et al. [57] and [PERSON] et al. [49] reported 18 and 13 missense variants, respectively. These mutations were commonly associated with neurodevelopmental phenotypes, including developmental delay, ASD, and sensory processing abnormalities. Representative examples include p.Arg102 Gln ([PERSON] et al. [58]), p.A704K ([PERSON] et al. [61]), and p.Asp12 Asn and p.Gly822 Ser ([PERSON] et al. [63]). Frameshift and nonsense mutations were each identified in 14 cases. Frameshift variants, described by [PERSON] et al. [63] and [PERSON] et al. [64], frequently resulted in premature termination of the SCN2A protein and were associated with intellectual disability and global developmental delay. Similarly, nonsense mutations, including five reported by [PERSON] et al. [65], were linked to a range of cognitive and behavioral impairments. Splicing mutations were observed in nine cases. [PERSON] et al. [59] described a novel splicing variant, c.2919+4 deIIT, which resulted in abnormal exon inclusion and was predicted to disrupt SCN2A channel function. This mutation was associated with low-functioning ASD and late-onset epilepsy. Structural deletions were reported in five individuals, most notably a 1.1 megabase deletion encompassing both _SCN2A_ and _SCN3A_, as documented by [PERSON] et al. [60]. This large-scale genomic alteration was associated with severe clinical phenotypes, including West syndrome and ASD. In addition, 10 single nucleotide variants were identified, primarily by [PERSON] et al. [63], who reported their association with specific ASD subtypes. [PERSON] et al. [56] reported a deletion variant, c.4550_4551 del, in a large cohort of Chinese individuals with ASD, highlighting the importance of population-specific genetic findings. In terms of inheritance patterns, de novo mutations were the most common, with 66 instances reported across the studies. These findings emphasize the largely sporadic nature of _SCN2A_-related conditions. [PERSON] et al. [49] described several de novo mutations, including Q1811E and M1548V. Mosaicism was observed in three cases, including presumed gonadal mosaicism in maternal half siblings, as described by [PERSON] et al. [65]. Most variants were heterozygous, with 49 instances reported, reflecting the clinical relevance of single-allele disruptions in _SCN2A_. These findings illustrate the complexity of the genetic landscape in _SCN2A_-related disorders. The wide range of variant types, including missense, nonsense, frameshift, splicing, and structural mutations, contributes to the broad phenotypic variability observed in affected individuals. \begin{table}
\begin{tabular}{l l l l l l l l l l l l l} \hline
**Reference** & **Mutation Type** & \multicolumn{2}{l}{**Homozygous**} & \multicolumn{2}{l}{**Maternal Inheritance**} & \multicolumn{2}{l}{**Unknown Origin**} & \multicolumn{2}{l}{**Mosaic**} & \multicolumn{2}{l}{**De Novo**} & \multicolumn{2}{l}{**Econ**} & \multicolumn{2}{l}{**Inton**} & \multicolumn{2}{l}{**CoF**} & \multicolumn{2}{l}{**Leef**} \\ \hline Alag