Targeted next generation sequencing identifies novel NOTCH3 gene mutations in CADASIL diagnostics patients

Table 3 Rare variants identified by NGS in the NOTCH3 gene. RefSeq NM_000435.2

Patient ID	Locus.	Ref	Location	Codon change	Protein change	PhyloP	SIFT	PolyPhen	LRT	MutationTaster	GERP++	AGVGD	PhD-SNP	dbSNP	MAF
C31	chr19:15281342	T	Ex27	c.4914A>G	WT (p.Glu1638Glu)	0.25				Poly				rs149222385	0.001
C13, C28, C33	chr19:15290236	G	Ex21	c.3399C>A	p.His1133Gln	−2.55	D	P (0.68)	NA	Poly	−8.6	C15	Neutral	rs112197217	0.005
C3, C12	chr19:15291576	C	Ex19	c.3058G>C	p.Ala1020Pro	0.57	T (0.19)	B (0.054)	N (0.006)	Poly	1.44	C25	Neutral	rs35769976	0.083
C3	chr19:15296513	C	In12			0.5				Poly				rs147014533	0.006
C3	chr19:15299048	G	Ex9	c.1490C>T	p.Ser497Leu	2.35	T (0.33)	B (0.036)	N (0.018)	D	5.04	C65	Neutral	rs114207045	0.006
C34	chr19:15299051	G	Ex9	c.1487C>T	p.Pro496Leu	2.35	T (0.1)	p (0.883)	N (0.007)	D	5.04	C65	Disease	rs11670799	0.005
C9	chr19:15302790	G	Ex4	c.660C>T	WT (p.Tyr220Tyr)	−1.85				D				rs114457076	0.001
C3	chr19:15308287	G	In2			−0.16				Poly				rs188132716	0.006
C16	chr19:15308288	G	In2			−0.98				Poly				rs202151374	0.003

PhyloP, SIFT, Polyphen-2, Mutation Taster, GERP++, AGVGD, and PhD-SNP are functional prediction scores in which increasing values indicate a more damaging effect except SIFT score <0.05 has damaging effect
Abbreviations: B benign, C conserved, D damaging or deleterious, Ex exon, In intron, NA not applicable, N not-conserved or neutral, P possible damaging, Poly polymorphic, T tolerated, WT wild type

ISSN: 1479-7364