Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability

Figures & data

Figure 1. (A) Family pedigree. Shaded shapes indicate affected individuals. (B) Next-gen sequence alignment of the SNAP25: c.142G > T (p.V48F alteration in the proband, mother, and father. (C) Sequence conservation plots at the mutated site amino acid position across different species.

Table 1. Variant filtering based on inheritance model and interpretation

	Post-Inheritance Model Filtering	Manual Review^a	Notable Candidate Genes^b
Autosomal Dominant Genes (Alterations)	22 (24)	4 (4)	1 (1)
Autosomal Recessive Genes (Alterations)	14 (30)	3 (6)	0 (0)
X-linked Recessive Genes (Alterations)	0 (0)	0 (0)	0 (0)
X-linked Dominant Genes (Alterations)	1 (1)	0 (0)	0 (0)
Y-linked Genes (Alterations)	N/A	N/A	N/A
Total Genes (Alterations)	37 (55)	7 (10)	1 (1)

^a Manual filtering involves the removal of genes unrelated to the patient's evaluated phenotype and alterations considered benign. ^bNotable Candidate Genes: Genes with disease phenotype association overlapping that of the proband.

Table 2. Summary of variants remaining after manual filtering

Autosomal Dominant
Gene Symbol/Model	Novel/Characterized Gene	Variant	Genotype			PolyPhen-2	SIFT	dbSNP	Allele Frequency		Comments
			Proband	Mother	Father				ESP	1000 Genomes
SNAP25	Novel	c.142G>T p.V48F	+/-	-/-	-/-	damaging	damaging	N/A	N/A	N/A	No LoF variants in ESP; few variants in ESP
FAM90A1	Novel	c.10del p.R4VfsX12	+/-	-/-	-/-	N/A	N/A	N/A	N/A	N/A	Many LoF variants in ESP, up to 144 alleles, homozygous fs changes
PCMTD1	Novel	c.921_922ins9 p.K307delins4	+/-	-/-	-/-	N/A	N/A	N/A	N/A	N/A	Pseudogenes, some pseudogenes with this 9 bp ins
SGK223	Novel	c.1029_1030ins8 p.C343WfsX28	+/-	-/-	-/-	N/A	N/A	N/A	N/A	N/A	Many LoF variants in ESP, up to 999 alleles, homozygous fs changes
Autosomal Recessive
Gene Symbol/Model	Novel/Characterized Gene	Variant	Genotype			PolyPhen-2	SIFT	dbSNP	Allele Frequency		Comments
			Proband	Mother	Father				ESP	1000 Genomes
ABCC10	Novel	c.1472G>A p.R491Q	+/-	+/-	-/-	benign	tolerated	rs141254177	0.02%	N/A
		c.2696G>A p.R899Q	+/-	-/-	+/-	benign	damaging	rs142010618	0.02%	N/A
CAPRIN2	Novel	c.1649A>G p.N550S	+/-	+/-	-/-	benign	tolerated	N/A	N/A	N/A
		c.1118G>A p.R373H	+/-	-/-	+/-	benign	tolerated	rs146283389	0.05%	0.09%
IGSF3	Novel	c.1945C>T p.R649C	+/-	-/-	-/-	damaging	damaging	rs139816559	N/A	N/A
		c.1379C>A p.P460Q	+/-	+/-	-/-	benign	damaging	rs147792935	0.06%	N/A

N/A, not available; blank boxes indicate not applicable