kvlqt1poly

KCNQ1 (KVLQT1)

Mutations - - Polymorphisms - - Locus Table

OMIM: *19250
AA numbering is based on Gene Bank cDNA: AF000571
Nucleotide numbering starts from ATG

Nucleotide Change	Aminoacid Change	Mutation Type	Region	Allele Frequncy	Phenotype	Reference
1-5t>c	Kozac variant	-	5'UTR	0.10 ⁽²⁾	N	Jongbloed et al. 2002
160-168dup	IAP54-56dup	Duplicarion	N-term	Black 1.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003; Abraham et al 2010
A328G	V110I	cSNP	N-term	Black 0.0 Asian 0.0 White 0.5 Hispanic 0.0	N	Ackerman et al 2003
G356A	G119D	cSNP	N-term			Koo SH et al 2006
G385A	V129I	cSNP	S1	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
387+217 C>T	not reported	SNP	S1 (exon 2a)	0.12 ⁽³⁾	N	Jongbloed et al. 2002
C435T	I145I	SNP	S1-S2	0.06	N	Itoh et al., 1998;Iwasa et al 2000
G459G	T153T	SNP	S1-S2	0.00375⁽¹⁾		Gouas et al. 2005
477+20 a>t		SNP	Intron 1	0.00125⁽¹⁾		Gouas et al. 2005
477+80 ins gg		SNP	Intron 1	0.31⁽¹⁾		Gouas et al. 2005
G619A	V207M	cSNP	S3	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
780+77 a>g	-	SNP	Intron 4	0.27⁽¹⁾		Gouas et al. 2005
	K218E	cSNP	S4	0.018	DITdP	Mank-Seymour 2006
C811T	L271L	SNP	S5 (exon6)	0.01 ⁽³⁾	N	Jongbloed et al. 2002; Gouas et al. 2005
G889A	G297S	cSNP	S5-pore	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
918+13 c>t		SNP	Intron 5	0.005⁽¹⁾		Gouas et al. 2005
C984T	I328I	SNP	S6	0.005⁽¹⁾		Gouas et al. 2005
T1003C	F335L	cSNP	S6	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
G1110A	A370A	SNP	C term	0.04⁽¹⁾ /0.01⁽²⁾	N	Iwasa et al 2000;
C1131G	T377T	SNP	C term	0.01 ⁽²⁾	N	Jongbloed et al. 2002
G1178T	K393N	cSNP	C-term	Black 0.0 Asian 0.0 White 1.1 Hispanic 0.0	N	Ackerman et al 2003; Mank-Seymour 2006
C1222G	P408A	cSNP	C-term	Black 2.3 Asian 0.0 White 0.0 Hispanic 1.1	N	Ackerman et al 2003
A1283G	D428G	cSNP	C-term	Black 0.0 Asian 0.0 White 0.5 Hispanic 0.0	N	Ackerman et al 2003
C1321T	P441S	cSNP	C-term	Black 0.0 Asian 0.0 White 0.5 Hispanic 1.1	N	Ackerman et al 2003
C1343G	P448R	cSNP	C term	0.25 ^{(3, 5)}	DITdP	Splawski et al. 2000; Ackerman et al 2003
G1352AA	R451Q	cSNP	C-term	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
IVS10-39 t>g	Intron10	SNP	C term	0.07 ⁽²⁾	N	Jongbloed et al. 2002
IVS10-16 c>t	Intron 10	SNP	C term	0.01 ⁽²⁾	N	Jongbloed et al. 2002
1394 -12 c>t	Intron 12	SNP	C term	0.04⁽¹⁾	N	Iwasa et al 2000
G1451C	S484T	cSNP	C term	0.01		Aydin et al 2005
1514+7 g>t	Intron 10	SNP	C term	0.005⁽¹⁾		Gouas et al. 2005
1514+14 g>t	Intron 10	SNP	C term	0.005⁽¹⁾		Gouas et al. 2005
1514 +46a>g	Intron 10	SNP	C term	0.44	may cause allelic dropout	Aydin et al 2005; Gouas et al. 2005; Tester et al 2006
1514+50 c>g	Intron 10	SNP	C term	0.01		Aydin et al 2005
1590+14 t>c	Intron 12	SNP	C term	0.08	N	Jongbloed et al. 2002 ; Gouas et al. 2005
A1476G	E492E	SNP	C term (exon 11)	0.01 ⁽²⁾		Jongbloed et al. 2002
G1556A	R519H	cSNP	C-term	Black 0.0 Asian 0.7 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
G1638A	S546S	SNP	C term	0.28⁽²⁾/ 0.20 ⁽⁷⁾	N	Lee et al., 1997;Iwasa et al 2000; Jongbloed et al. 2002; Aydin et al 2004
IVS13+36 g>a	Intron 13	SNP	C term	/0.32⁽⁷⁾	N	Jongbloed et al. 2002; Aydin et al 2004
1732 +43 t>c	Intron 13	SNP	C term	0.23⁽¹⁾/ 0.20 ⁽²⁾/ 0.20 ⁽⁷⁾ /0.26	N	Iwasa et al 2000; Jongbloed et al. 2002; Aydin et al 2004; Gouas et al. 2005
1794+32 g>t	Intronn 14	SNP	C term	0.06 ⁽²⁾/ 0.07⁽⁷⁾/ 0.05 ⁽¹⁾	may cause allelic dropout	Jongbloed et al. 2002; Aydin et al 2004; Gouas et al. 2005; Tester et al 2006
G1638A	S546S	SNP	C-term	0.21⁽¹⁾		Gouas et al. 2005
1685 +23 g>a	Intron 15	SNP	C term	0.04⁽¹⁾	N	Iwasa et al 2000

G1861A	G621S	cSNP	C-term	Black 0.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
C1986T	Y662Y	SNP	C term (exon 16)	0.35 ⁽²⁾ /0.25⁽¹⁾	N	Jongbloed et al. 2002; Gouas et al. 2005
G1927A	G643S ⁽⁴⁾	cSNP	C term	0.09^{(1, 6)}	effect shown⁽⁴⁾	Itoh et al., 1998; Iwasa et al 2000; Ackerman et al 2003
G1942A	V648I	cSNP	C-term	Black 2.3 Asian 0.0 White 0.0 Hispanic 0.0	N	Ackerman et al 2003
	R1047L	cSNP	C-term	Black 0.3 Asian 0.0 White 3.7 Hispanic 0.0	N	Ackerman et al 2003
2031+479 c>t	3'UTR	SNP	-	0.06⁽¹⁾		Gouas et al. 2005
2031+875 a>g	3'UTR	SNP	-	0.30⁽¹⁾		Gouas et al. 2005
2031+932 a>g	3'UTR	SNP	-	0.32⁽¹⁾		Gouas et al. 2005

N= normal ; cSNP = coding SNP/non synonomous polymorphism.

(1) Frequency of the uncommon variant.
(2) het=Frequency of heterozygous carriers after Jongbloed et al. 2002.
(3) Yang et al Circulation 2002 reported a 20-35% frequency among japanese population. Functional data are still lacking thus, at the present time it is not known if mild current alterations are associated with such variant (see note (1)).
(4) This variant has been associated with an IKs current abnormalities by Kubota et al ., thus possibly causing a mild form of LQTS or predisposition to drug-induced Torsades de Pointes.
(5) Allele frequencies of P448R according to Ackerman et al: Black 0.3; Asian 16.4; White 0.0; Hispanic 0.0.
(6) Allele frequencies of G643S according to Ackerman et al: Black 5.9; Asian 6.0; White 0.0; Hispanic 1.1
(7) Allele frequencies of G6S546S43S according to Aydin et al 2004