TABLE 2.

Spectrum of NOTCH3 variants found in 38 Chinese CADASIL patients.

Nucleotide change	Amino acid change	Exon	EGFr domain	Cysteine affecting (Y/N)b	Frequency	Variants per exon [No. (%)]	Reported in CADASIL (Y/N)c	GOM deposit in biopsyd	ACMGe
224 G > C	R75P	3	1	N	1	10.53%	Y	NP*	LP
268 C > T	R90C	3	2	Y	1		Y	1/1	P
328 C > T	R110C	3	2	Y	2		Y	1/1	LP
397 C > T	R133C	4	3	Y	2	26.32%	Y	1/1	P
397 C > A	R133S	4	3	N	1		Y	1/1	LP
457 C > T	R153C	4	3	Y	3		Y	0/2	P
505 C > T	R169C	4	4	Y	1		Y	1/1	P
544 C > T	R182C	4	4	Y	2		Y	2/2	P
554 G > A	C185Y	4	4	Y	1		Y	1/1	P
709 G > A	V237M	5	5	N	2	5.26%	Y	NP	U
1013 G > C	C338S	6	8	Y	1	2.63%	Y	NP	P
1630 C > T	R544C	11	13/14	Y	9	34.21%	Y	2/2	LP
1759 C > T	R587C	11	15	Y	1		Y	NP	U
1819 C > T	R607C	11	15	Y	2		Y	NP	LP
1820 G > A	R607H	11	15	N	1		Y	1/1	LP
2299 C > T	R767C	15	19	Y	1	2.63%	Y	NP	U
3016 C > T	R1006C	19	26	Y	1	5.26%	Y	NP	LP
3062 A > G	Y1021C	19	26	Y	1		Y	NP	U
3299 G > A	R1100H	20	28	N	1	2.63%	Y	NP	U
4039 G > C	G1347R	24	34	N	1	2.63%	Y	NP*	U
5282 G > A	R1761H	29	Na	N	1	2.63%	Y	NP*	U
5764 G > T	V1922L	31	Na	N	1	2.63%	N	NP	U
6608 C > A	S2203Y	33	Na	N	1	2.63%	N	NP	U

^aY, in EGFr region; N, outside EGFr region. ^bY, cysteine affecting; N, cysteine sparing. ^cY, variant reported in CADASIL; N, novel variant in CADASIL. ^dGOM-detected proband/studied proband; NP, skin biopsy not performed in present study; NP*, skin biopsy was not performed in present study but GOM deposit was reported in literature. ^eInterpretation of variants based on consensus recommendation of the American College of Medical Genetics (ACMG): pathogenic (P), likely pathogenic (LP), and unknown significance (U).