A novel stop-gain pathogenic variant in FLT4 and a nonsynonymous pathogenic variant in PTPN11 associated with congenital heart defects

Tabib, Avisa; Talebi, Taravat; Ghasemi, Serwa; Pourirahim, Maryam; Naderi, Niloofar; Maleki, Majid; Kalayinia, Samira

doi:10.1186/s40001-022-00920-8

Table 2 Bioinformatics analysis of pathogenic reported variants in PTPN11 (NM_002834) related to congenital heart defects

From: A novel stop-gain pathogenic variant in FLT4 and a nonsynonymous pathogenic variant in PTPN11 associated with congenital heart defects

No.	Exon	HGVS DNA	HGVS protein	Chromosome 12 position (hg19)	dbSNP	CADD	SIFT	Polyphen-2	PROVEAN	MutationTaster	ClinVar	Condition (CHD or cardiomyopathy)	Refs.
1	1	c.5C > T	p.T2I	112,856,920	rs267606990	23.8	T	B	N	DC	P	NS (PS)	[40]
2	2	c.124A > G	p.T42A	112,884,189	rs397507501	22.7	T	PD	D	DC	P	NS (PS, ASD)	[40,41]
3	3	c.184 T > G	p.Y62D	112,888,168	rs121918460	24.9	D	PD	D	DC	P	NS (AVCD, ASD, PS), PST, PDA	[40,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44]
4	3	c.188A > G	p.Y63C	112,888,172	rs121918459	28.1	D	PD	D	DC	P	NS (AVCD, HCM, PS)	[40,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]
5	3	c.215C > G	p.A72G	112,888,199	rs121918454	23.7	D	PD	D	DC	P	NS (HCM, PS)	[40,41]
6	3	c.A236C	p.Q79P	112,888,220	NA	24.0	D	PD	D	DC	NA	NS (PS)	[40,43]
7	3	c.317A > C	p.D106A	112,888,301	rs397507517	25.3	D	PD	D	DC	P	NS (ASD, PS)	[40,41,43,45]
8	7	c.836A > G	p.Y279C	112,910,827	rs121918456	28.9	D	PD	D	DC	P	LS (PVS, HCM), NS (PS,HCM)	[40,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,46,47,48]
9	8	c.922A > G	p.N308D	112,915,523	rs28933386	23.6	D	PD	D	DC	P	NS (PS, HCM,VSD)	[40,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,49,50]
10	8	c.923A > G	p.N308S	112,915,524	rs121918455	22.7	T	PD	D	DC	P	PS, NS (HCM)	[40,41,51]
11	12	c.1403C > T	p.T468M	112,926,270	rs121918457	28.7	D	PD	D	DC	P	LS (HCM, AVCD), NS (PS, HCM)	[40,41,46,47,48]
12	13	c.1508G > C	p.G503A	112,926,888	rs397507546	27.4	T	PD	D	DC	P	NS (PS)	[40]
13	13	c.1510A > G	p.M504V	112,926,890	rs397507547	26.8	T	PD	D	DC	P	NS (PS,HCM)	[40,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]
14	14	c.1678C > T	p.L560F	112,940,026	rs397516797	22.7	D	B	N	DC	LB	NS (HCM)	[40]
15	5	c.540C > T	p.D180 =	112,892,382	rs753269427	9.256	T	NA	N	DC	LB	CHD	[52]
16	2	c.127C > T	p.L43F	112,884,192	NA	27.8	D	PD	D	DC	NA	CHD	[52]
17	3	c.155C > T	p.T52I	112,888,139	rs397507503	28.0	D	PD	D	DC	P	NS (PS)	[41]
18	3	c.172A > G	p.N58D	112,888,156	rs397507505	26.6	T	PD	D	DC	P	NS (PS)	[41,51]
19	3	c.172A > C	p.N58H	112,888,156	rs397507505	25.7	T	PD	D	DC	P	NS (PS)	[41]
20	3	c.174C > A	P.N58K	112,888,158	rs397507506	25.0	T	PD	D	DC	P	NS (PS)	[41]
21	3	c.179G > C	p.G60A	112,888,163	rs397507509	26.5	D	PD	D	DC	P	NS (PS, ASD)	[41,43]
22	3	c.178G > A	p.G60S	112,888,162	rs397507507	29.7	D	PD	D	DC	P	NS (PS)	[41]
23	3	c.182A > G	p.D61G	112,888,166	rs121918461	28.2	D	PD	D	DC	P	NS (PS,ASD)	[41,43]
24	3	c.181G > A	p.D61N	112,888,165	rs397507510	32	D	PD	D	DC	P	ASD, NS (PS)	[41,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,51]
25	3	c.214G > T	p.A72S	112,888,198	rs121918453	25.0	D	PD	D	DC	P	NS (PS,HCM)	[41,51]
26	3	c.218C > T	p.T73I	112,888,202	rs121918462	27.4	D	PD	D	DC	DC	NS (PS,ASD)	[41,43]
27	3	c.217_218delinsCT	p.T73L	112,888,201	rs397516802	28.0	D	PD	D	DC	P	NS (PS)	[41]
28	3	c.228G > C	p.E76D	112,888,212	rs397507514	22.3	D	PD	D	DC	P	NS	[41,51]
29	3	c.236A > G	p.Q79R	112,888,220	rs121918466	26.0	D	PD	D	DC	P	NS (PS)	[41,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43]
30	4	c.328G > A	p.E110K	112,888,312	rs397507518	32	D	PD	D	DC	P	NS	[41]
31	4	c.417G > C	p.E139D	112,891,083	rs397507520	25.0	D	PD	D	DC	P	NS (PS), HIS	[41,53]
32	7	c.767A > G	p.Q256R	112,910,758	rs397507523	24.3	T	B	D	DC	P	NS (PS)	[41]
33	7	c.781C > T	p.L261F	112,910,772	rs397507525	22.6	T	B	N	DC	P	NS	[41]
34	7	c.802G > T	p.G268C	112,910,793	rs397507527	31	D	PD	D	DC	P	NS	[41]
35	7	c.844A > G	p.I282V	112,910,835	rs397507529	23.4	T	B	N	DC	P	NS (PS)	[41]
36	7	c.853 T > C	p.F285L	112,910,844	rs397507531	32	D	PD	D	DC	P	NS (PS)	[41]
37	8	c.854 T > G	p.F285C	112,915,455	rs121918463	32	D	PD	D	DC	P	NS (PS)	[41]
38	8	c.854 T > C	p.F285S	112,915,455	rs121918463	32	D	PD	D	DC	P	NS (PS),VSD, ASD	[41,51,53]
39	12	c.1381G > T	p.A461S	112,926,248	rs121918468	32	D	PD	D	DC	P	NS (HCM)	[41]
40	12	c.1381G > A	p.A461T	112,926,248	rs121918468	32	D	PD	D	DC	P	NS (HCM)	[41]
41	13	c.1471C > T	p.P491S	112,926,851	rs397507539	23.1	T	B	N	DC	P	NS (PS)	[41]
42	13	c.1471C > A	p.P491T	112,926,851	rs397507539	23.1	T	PD	N	DC	P	NS (PS)	[41]
43	13	c.1504 T > G	p.S502A	112,926,884	rs121918458	26.9	T	PD	D	DC	P	NS (PS)	[41]
44	13	c.1505C > T	p.S502L	112,926,885	rs397507544	32	T	PD	D	DC	P	NS (PS)	[41]
45	13	c.1528C > G	p.Q510E	112,926,908	rs397507549	26.5	D	PD	D	DC	P	NS (PS, HCM),VSD	[41,48,54]
46	13	c.1529A > C	p.Q510P	112,926,909	rs121918470	27.9	D	PD	D	DC	P	NS (PS)	[41]
47	13	c.1529A > G	p.Q510R	112,926,909	rs121918470	27.5	D	PD	D	DC	P	NS (PS, HCM)	[41,42]
48	3	c.166A > G	p.I56V*	112,888,150	rs397507504	23.6	D	PD	N	DC	P	HCM	[42]
49	3	c.205G > C	p.E69Q	112,888,189	rs397507511	25.5	D	PD	D	DC	P	NS	[42,45]
50	7	c.846C > G	p.I282M*	112,910,837	rs397507530	23.2	D	PD	D	DC	P	NS	[42]
51	3	c.181G > C	p.D61H	112,888,165	rs397507510	29.2	D	PD	D	DC	P	NS (AVSD)	[53]
52	13	c.1472C > T	p.P491L	112,926,852	rs397507540	23.7	T	PD	D	DC	P	NS	[45]
53	3	c.317A > G	p.D106G	112,888,301	NA	29.3	D	PD	D	DC	P	NS	[45]
54	13	c.1492C > T	P.R498W	112,926,872	rs397507541	31	D	PD	D	DC	P	LS (HCM)	[46]
55	13	c.1493G > T	P.R498L	112,926,873	rs397507542	31	D	PD	D	DC	P	LS (HCM)	[46]
56	13	c.1517A > C	P.Q506P	112,926,897	rs397507548	27.2	D	PD	D	DC	P	LS (PS)	[46]
57	7	c.836A > C	P.Y279S	112,910,827	rs121918456	27.7	D	PD	D	DC	P	LS (HCM)	[46,47]
58	7	c.853 T > A	p.F285I	112,910,844	rs397507531	32	D	PD	D	DC	P	NS	[51]
59	12	c.1391G > C	p.G464A	112,926,258	rs121918469	28.4	D	PD	D	DC	P	NS	[51]
60	13	c.1507G > A	p.G503R	112,926,887	rs397507545	31	T	PD	D	DC	P	NS (PS)	[41,51]
61	13	c.1508G > A	p. G503E	112,926,888	rs397507546	29.3	T	PD	D	DC	P	NS (PS)	[51]
62	13	c.1510A > T	p.M504L	112,926,890	NA	23.3	T	B	N	DC	NA	NS	[51]
63	13	c.1471C > G	p.P491A	112,926,851	rs397507539	22.6	T	B	N	DC	P	NS (PS, ASD)	[49]
64	13	c.1530G > C	p.Q510H	112,926,910	rs397507550	24.5	D	PD	D	DC	P	LS (PS, ASD, HCM)	[54,55]
65	13	c.1510A > C	p.M504L	112,926,890	NA	23.1	T	B	N	DC	NA	NS	[43]

CHD congenital heart disease, NS Noonan syndrome, LS LEOPARD syndrome, PS pulmonary valve stenosis, ASD atrial septal defects, VSD ventricular septal defect, AVSD atrioventricular septal defect, AVCD atrioventricular canal defect, PST paroxysmal supraventricular tachycardia, PDA patent ductus arteriosus, HCM hypertrophic cardiomyopathy, PVS pulmonary vein stenosis, HIS hypertrophy interventricular septum, DC disease causing, D deleterious, T tolerated, N neutral, B, benign, PD probably damaging, P pathogenic, B benign, NA not available/not applicable
CADD, Phred ≤ 20: damaging; Phred > 20: natural
SIFT, score ≤ 0.05: deleterious; score > 0.05: tolerable
Polyphen-2, score = 0–0.15: benign; score = 0.15–0.85: possibly damaging; score = 0.85–1: probably damaging
PROVEAN, score ≤ − 2.5: deleterious; score > − 2.5: natural

Back to article page

ISSN: 2047-783X

Contact us

Submission enquiries: jacinth.kennady@springernature.com
General enquiries: info@biomedcentral.com

European Journal of Medical Research

Contact us