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.