Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing

Table 3 Characteristics of the novel missense mutations unique to the Swedish cohort

Gene	Exon	Nucleotide change	Amino acid change	Region	GD	SIFT	PolyPhen	Align-GVGD	Segregation analysis
*KCNQ1*	3	c.506C>G	p.T169R	S2	71	not tolerated	Possibly damaging	C0	de novo
	3	c.509A>G	p.E170G	S2-S3	98	not tolerated	Probably damaging	C0	Yes
	5	c.734G>T	p.G245V	S4-S5	109	not tolerated	Probably damaging	C0	Borderline
	7	c.973G>T	p.G325W	S6	184	not tolerated	Probably damaging	C65	Yes
*KCNH2*	2	c.182A>G	p.Q61R	PAS	43	not tolerated	Possibly damaging	C0	de novo
	2	c.284A>G	p.E95G	PAC	98	not tolerated	Probably damaging	C0	de novo
	5	c.1094A>G	p.E365G	N-term	98	not tolerated	Possibly damaging	C0	Yes
	7	c.1706A>G	p.Y569C	S5	194	not tolerated	Probably damaging	C65	Borderline
	9	c.2312A>G	p.H771R	cNBD	29	not tolerated	Probably damaging	C25	N/A
*SCN5A*	2	c.86C>T	p.A29V	N-term	65	not tolerated	Probably damaging	C65	Yes
	22	c.3893C>T	p.P1298L	DIII-S4	98	not tolerated	Possibly damaging	C65	N/A

GD, Grantham distance ordered from largest difference (GD=215) between the substituted amino acids to no difference (GD=0); SIFT, sorting intolerant from tolerant; PolyPhen, Polymorphism Phenotyping predicting variants as probably damaging, possibly damaging or benign; Align-GVGD, Align Grantham variation and Grantham distance ordered from most likely (C65) to interfere with function to least likely (C0); Segregation analysis: Yes, segregation demonstrated; de novo, mutation not present in either parent; Borderline, non-penetrant or borderline QTc; N/A, samples not available or missing data.

ISSN: 1471-2261