Fig 1: PTC variants of neurological disease and positionally agnostic rescue of UGA PTC stop codons in SYNGAP1 and CDKL5. (A) PTC landscape for a variety of neurological and neurodevelopmental disorders. Prevalence varies from 13% (SCN2A) to 42% (CHD2), with a majority caused by Arg CGA-to-TGA. (B) ClinVar submissions by stop codon type further demonstrate ArgUGA as the dominant PTC. (C) Experimental layout to measure agnostic ArgUGA PTC rescue in SYNGAP1 and CDKL5 across 19 variants from two genes: SYNGAP1 (R76, R84, R105, R485, R520, R526, R628, R716, R863, R908, R1026, and R1181) and CDKL5 (R59, R134, R550, R559, R952, R970, and R981). (D, E) Positional agnostic rescue in SYNGAP1 and CDKL5. Only one site, R134TGA in CDKL5, demonstrated poor rescue, possibly owing to the position of this residue within a particularly complex protein fold within the CDKL5 kinase domain. Data were analyzed using multiple unpaired t-tests with Holm-Sidak correction (P < .00001, n = 4 per construct). Created in BioRender. Al saneh, A. (2026) https://BioRender.com/2ce96kj.