Table 3.

Selected Genetic Polymorphisms Identified in Genes Linked with Heart Development and Associated with Non-Syndromic Congenital Heart Defects

Gene	Nucleotide/Protein change	Effect	Phenotype	Population	Reference
IRX1	p.Gln240Glu p.Ser298Asn p.Ala381Glu	Non-synonymous	TrA, TGA	Asian (Chinese)	Guo et al. (2017)
PITX2	p.R91Q p.T129S	Loss-of-function mutation	TGA, VSD	Asian (Chinese)	Panepistēmio tēs Krētēs. et al. (2014)
HAND2	p.L47P	Loss-of-function mutation	TOF	Asian (Chinese)	Lu et al. (2016)
GATA4	c.431C4T p.Ala144Val	Possibly damaging	PA, ASD	Asian (Japanese)	Yoshida et al. (2016)
	c.1064C > G, T355S c.1129A > G, S377G c.1138G > A, V380 M c.1180C > A, P394T c.1273G > A, D425 N	Missense	ASD, VSD, PDA, DORV, TOF, PS	Asians (Indians)	Bose et al. (2017)
	c.788 C > G	Missense	VSD	Asian (Chinese)	Xiong et al. (2013)
GATA6	p.D404Y p.E460X	Decreased transactivation activity	TOF, VSD	Asian (Chinese)	Wang et al. (2012)
	c.151G>A/(E51K), c.551G>A/(S184 N) c.733G>C/(G245R),	Reduction in the transactivation capacity of downstream genes	TOF, TrA	Asian (Chinese)	Lin et al. (2010); Wang et al. (2014)
NR2F2	c.220_222dup/p.Gln75dup c.1022C>A/p.Ser341Tyr c.614A>T/p.Asn205Ile c.753G>C/p.Glu251Asp c.1234G>T/p.Ala412Ser c.509A>T/p.Asp170Val c.970þ1G>A (14;15)(q23;q26.3)	Reductions in transcriptional activity	TOF, AVSD, CoA,	Caucasians	Al Turki et al. (2014)
PRDM6	c.1646G>A/p.Arg549Gln c.788G>C/p.Cys263Ser c.1385A>G/p.Gln462Arg	Epigenetic regulation of ductus remodeling	PDA	Caucasians	Li et al. (2016a)
FOXC1	Copy number variation		CoA	Caucasians	Sanchez-Castro et al. (2016)
TFAP2B	c.601 + 5G>A c.435_438delCCGG		PDA	Asian (Chinese)	Chen et al. (2011)
	c.1006 G > A		TOF, PA, PDA	Asian (Chinese)	Xiong et al. (2013)
NKX2-5	1433A>G	Affects septation during cardiac morphogenesis and maturation and maintenance of the atrioventricular node	TOF PLSVC, BAV	Asian (Chinese) Caucasians	Cao et al. (2015); Cao et al. (2016); Dargis et al. (2016)
	c.608A>G/p.E203G c.646C>T/p.R216C c.852G>A/p.N226D 1212G>T (3′UTR)		VSD	Asian (Indians)	Dinesh et al. (2010)
	p.K192X	No transcriptional activity	BAV	Asian (Chinese)	Qu et al. (2014)
NKX2.6	c.454A>C/p.K152Q	Reduced its transcriptional activating function	VSD	Asian (Chinese)	Li et al. (2016b)
TBX5	c.322C>A/p.Pro108Thr c.791G>A/p.Arg264Lys	Affect protein function	TrA VSD, PA	Asian (Japanese)	Yoshida et al. (2016)
TBX20	c.991A>G p.Thr331Ala	Possibly damaging	VSD	Asian (Japanese)	Yoshida et al. (2016)
CITED2	c.550G > A, Gly184Ser c.574A > G, Ser192Gly c.573-578del6, Ser192fs	Non-synonymous	MD, RAA, TOF AS AS, PVS, VSD, ASD	Asian (Chinese)	Xu et al. (2014)
	c.428 G > C p.Gly143Ala	Non-synonymous	PDA	Asian (Chinese Tibetan)	Liu et al. (2017)
	c.508_534del27 p.Ser170_Gly178del c.534_535ins27 p.Gly178_Ser179ins9 c.592_597delAGCGGC p.Ser198_Gly199del	Non-synonymous	VSD, ASD	Caucasians	Sperling et al. (2005)
	c.C418T, p. P140S c.C548T p. S183 L c.A586G p. S196G c.481–483delAGC p.Ser161delAGC c.574–579delAGCGGC p.Ser192_Gly193delAGCGGC	Non-synonymous	ASD, VSD	Asian (Chinese)	Liu et al. (2014)
FOXP1	c.1702C>T, p.Pro568Ser	Non-synonymous	AVSD	Caucasian	Chang et al. (2013)
MYH6	E501Stop, A230P IVS37-2A.G, R1116S, A1443D, R1865Q H252Q V700 M A1366D	Non-sense mutation, Splice site mutation, Missense mutations	TrA ASD TGA PFO AS	Caucasians	Granados-Riveron et al. (2010)
	c.50G>A, R17H c.1615T>C, C539R c.1628A>G, K543R	missense mutations	ASD	Caucasians	Posch et al. (2011)
ZFPM2/FOG2	p.V339I, p.A426 p.M703 L, p.T843 M	Non-synonymous	DORV TOF	Asian (Chinese)	Zhang et al., 2014); Qian et al. (2017)
	c. 972C>G, H324Q c. 3442G>A, E1148 K	Non-synonymous	TOF TOF/PFO	Asian (Chinese)
ACTC1	c.251T>C, p.Met84Thr p.Glu101Lys p.Met125Val	Non-synonymous	ASD, VSD, PS,	Lebanese	Augiere et al. (2015)