. 2014 Nov 1;18(11):722–735. doi: 10.1089/gtmb.2014.0109

Table 5.

Summary of Pathogenic Mutations Detected by Next-Generation Sequencing

Exon	Genomic mutation	Amino acid substitution	Type of mutation	Reference	Age	Familial	Symptoms	Variations of unknown significance in rasopathy genes	Number of mutations in other genes
2	c.83_84insG	p.Asn29Glufs^*9	Frameshift		68	Yes	P,N	RASA1 c.293C>T p.Ala98Val	2
3	c.264_265insA	p.Thr89Asnfs^*18	Frameshift		44	Yes	P,B,N		1
5	c.491T>A	p.Leu164^*	Nonsense		50	Yes	P,B,O,N		1
5	c.495-498delTGTT	p.Cys167Glnfs^*10	Frameshift		41	No	P,N,L		1
5	c.499_500insG	p.Cys167Trpfs^*7	Frameshift		27	No	P,B,N,L		1
5	c.574C>T	p.Arg192^*	Nonsense		32	No	P,N,L		2
10	c.1105C>T	p.Gln369^*	Nonsense		40	Yes	P,N,L		1
11	c.1241T>G	p.Leu414Arg	Missense^a	Lee et al. (2006)	21	No	P,N,L		1
11	c.1246C>T	p.Arg416^*	Nonsense		32	Yes	P,B,N		1
12	c.1381C>T	p.Arg461^*	Nonsense		3	No	P	RASA1 c.669G>C p.Gln223His	1
12	c.1381C>T	p.Arg461^*	Nonsense		67	Yes	P,B,N		1
12	c.1381C>T	p.Arg461^*	Nonsense		41	Yes	P,B,N		0
13	c.1466A>G	p.Tyr489Cys	Missense^a	Messiaen et al. (2000)	36	No	P,N		1
13	c.1466A>G	p.Tyr489Cys	Missense^a	Messiaen et al. (2000)	63	Yes	P,B,N		0
13	c.1466A>G	p.Tyr489Cys	Missense^a	Messiaen et al. (2000)	71	No	P,N,L		1
13	c.1527+1_+4delGTAA		Splicing		30	No	P,N,L		2
14	c.1541_1542delAG	p.Gln514Argfs^*43	Frameshift		52	No	P,B,N		1
15	c.1721+3A>G		Splicing	Purandare et al. (1994)	40	Yes	P,B,N		0
16	c.1726C>T	p.Gln576^*	Nonsense		36	No	P,N		0
16	c.1754_1757delACTA	p.Thr586Valfs^*18	Frameshift		49	Yes	P,N		0
16	c.1765C<T	p.Gln589^*	Nonsense		40	No	P,N		1
16	c.1832delT	p.Asn614Ilefs^*17	Frameshift		80	No	P,N,L		3
17	c.1876_1877insT	p.Tyr628Leufs^*6	Frameshift		79	Yes	P,B,N,L		2
17	c.1885G>A	p.Gly629Arg	Missense^a	Gasparini et al. (1996)	57	Yes	P,N		2
18	c.2041C>T	p.Arg681^*	Nonsense		23	No	P,N		1
18	c.2041C>T	p.Arg681^*	Nonsense		35	Yes	P,B,N		1
18	c.2087G>A	p.Trp696^*	Nonsense		58	Yes	P,B,N,L		0
18^b	c.2183T>G	p.Val728Gly	Missense		67	Yes	P,N		0
21	c.2423delT	p.His809Thrfs^*12	Frameshift		43	Yes	P,N		1
21	c.2540T>C	p.Leu847Pro	Missense^a	Fahsold et al. (2000)	33	Yes	P,N,L		0
21	c.2540T>C	p.Leu847Pro	Missense^a	Fahsold et al. (2000)	59	Yes	P,B,N,L		0
21^b	c.2540T>G	p.Leu847Arg	Missense		55	No	P,N		0
21	c.2446C>T	p.Arg816^*	Nonsense		52	Yes	P,N,L		0
22	c.2851-5_-2delTTTA		Splicing		19	No	P,B,N,L		1
23	c.3048T>A	p.Cys1016^*	Nonsense		50	Yes	P,B,N		0
24	c.3132C>A	p.Tyr1044^*	Nonsense		12	Yes	P,O,N		0
25	c.3213_3214delAA	p.Ser1072Hisfs^*16	Frameshift		29	No	P,N,L		2
27	c.3595_3596insGG	p.Thr1199Argfs^*17	Frameshift		20	No	P,N,L		1
27	c.3615_3616delTG	p.Phe1205Leufs^*12	Frameshift		37	Yes	P,B,N		2
27	c.3615_3616delTG	p.Phe1205Leufs^*12	Frameshift		64	Yes	P,B,N,L		1
28	c.3709-2A>G		Splicing		44	No	P,B,N,L		0
28	c.3765_3766insCT	p.Leu1257Cysfs^*10	Frameshift		29	No	P,B,N,L		2
28	c.3826C>T	p.Arg1276^*	Nonsense		21	No	P,O,B,N,L		0
29	c.3888T>A	p.Tyr1296^*	Nonsense		49	No	P,N,L		0
30	c.4084C>T	p.Arg1362^*	Nonsense		27	No	P,N		1
32	c.4329delA	p.Lys1444Argfs^*25	Frameshift		50	Yes	P,B,N,L		0
32	c.4330A>G	p.Lys1440Glu	Missense^a	Li et al. (1992)	40	No	P,N,L		0
33	c.4430+1G>A		Splicing		49	Yes	P,B,N		2
34	c.4544delA	p.Gln1515Argfs^*59	Frameshift		35	Yes	P,N		2
35	c.4716_4724+6 delTATGACTAGGTAAAG		Splicing		50	No	P,B,N,L		1
36	c.4743_4744delAG	p.Glu1582Argfs^*39	Frameshift		36	No	P,B,N,L		2
36	c.4769T>G	p.Leu1590^*	Nonsense		45	No	P,N		1
37	c.4873_4874insA	p.Tyr1625^*	Nonsense		63	No	P,B,N		1
37	c.5198T>G	p.Leu1733^*	Nonsense		40	No	P,B,N,L		1
38	c.5269-6_5276delTTCCAGGTTGGTTC		Splicing		38	No	P,N,L		1
38	c.5269-1G>A		Splicing		39	Yes	P,B,N,L		0
38	c.5516_5517insC	p.Glu1841Profs^*21	Frameshift		31	Yes	P,B,N		1
38	c.5609G>A	p.Arg1870Gln	Missense^a	Ars et al. (2003)	69	Yes	P,B,N		0
40	c.5902C>T	p.Arg1968^*	Nonsense		22	No	P,N		1
44	c.6675G>A	p.Trp2225^*	Nonsense		54	No	P,O,B,N		3
45	c.6772C>T	p.Arg2258^*	Nonsense		69	Yes	P,N		0
45	c.6772C>T	p.Arg2258^*	Nonsense		52	Yes	P,B,N,L		1
45^b	c.6818A>T	p.Lys2273Met	Missense		46	No	P,N		1
46	c.6850_6853delACTT	p.Tyr2285Thrfs^*5	Frameshift		42	Yes	P,N		1
46	c.6853_6854insA	p.Tyr2285^*	Nonsense		21	No	P,N		0
46	c.6853_6854insA	p.Tyr2285^*	Nonsense		28	No	P,N		0
46	c.6904C>T	p.Gln2302^*	Nonsense		37	Yes	P,N,L		1
47	c.6950G>A	p.Trp2317^*	Nonsense		25	No	P,B,N,L		0
50	c.7348C>T	p.Arg2450^*	Nonsense		46	No	P,B,N,L		0
54	c.7970+1_+4delGTAA		Splicing		41	Yes	P,N,L		2
			ex1 to 58 deletion		13	No	P,N,L		3
			ex1 to 58 deletion		29	No	P,N		1
			ex1 to 58 deletion		68	No	P,N		1
			ex1 to 58 deletion		58	No	P,B,N,L		1
			ex1 to 58 deletion		34	No	P,B,N		1
			ex1 deletion		68	No	P,N,L		1
			ex3 to 4 deletion		59	No	P,N,L		0
			ex6 to 51 deletion		36	Yes	P,N,L		2
			ex8 deletion		28	Yes	P,N		0
			ex12 deletion		55	No	P,N		1
					37	No	P		0
					50	No	P,N		0
					45	Yes	P,N,L		2
					30	No	P,N		0
					34	Yes	P,B,N		1
					25	No	P		0

^{^a}

Previously reported to cause aberrant splicing.

^{^b}

Predicted to be pathogenic by bioinformatics programs.

Symptoms: P, pigment; O, optic nerve tumor; B, bone manifestation; N, neurofibroma; L, Lisch nodules; HGMD; Human Genome Mutation Database.