Table 2. List of Variants and Their Threshold Effect Coefficients c.
| Gene | Variant Effect on Model Parameters | Threshold Effect |
|---|---|---|
| CACNA1C | Voffm*,CaHVA: −25.9 mV; Voffh*,CaHVA: −27.0 mV | c = .094 |
| CACNA1C | Voffm*,CaHVA: −37.3 mV; Voffh*,CaHVA: −30.0 mV | c = .060a |
| CACNB2 | Voffh*,CaHVA: −5.2 mV; Vsloh*,CaHVA: × .69 | c = .582 |
| CACNB2 | τh*,CaHVA: × 1.7 | c ≥ 2.000 |
| CACNB2 | Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × .6 | c = .310 |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × .6 | c = .154 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × .6 | c = .205 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × .6 | c = .675b | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × .6 | c = .814 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × .6 | c = .057 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × .6 | c = .517 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × .6 | c = .078 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × 1.66 | c = .275 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × 1.66 | c = .188 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × 1.66 | c = .190 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × .6; τh*,CaHVA: × 1.66 | c = 1.687 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × 1.66 | c = .707 | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: −5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × 1.66 | c = .061 | |
| Voffm*,CaHVA: −4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × 1.66 | c = .457a,c | |
| Voffm*,CaHVA: +4.9 mV; Voffh*,CaHVA: +5.1 mV; τm*,CaHVA: × 1.68; τh*,CaHVA: × 1.66 | c = .084 | |
| CACNA1D | Voffm*,CaHVA: −10.9 mV; Vslom*,CaHVA: × .73; Voffh*,CaHVA: −3.0 mV; Vsloh*,CaHVA: × .81; τh*,CaHVA: × 1.25 | c = .118 |
| Voffm*,CaHVA: −10.9 mV; Vslom*,CaHVA: × .73; Voffh*,CaHVA: +3.5 mV; Vsloh*,CaHVA: × .81; τh*,CaHVA: × 1.25 | c = .106 | |
| CACNA1D | Voffm*,CaHVA: −10.6 mV; Vslom*,CaHVA: × .8; Voffh*,CaHVA: −5.3 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .114 |
| Voffm*,CaHVA: +3.4 mV; Vslom*,CaHVA: × .8; Voffh*,CaHVA: −5.3 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = 1.962 | |
| Voffm*,CaHVA: −10.6 mV; Vslom*,CaHVA: × 1.12; Voffh*,CaHVA: −5.3 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .131 | |
| Voffm*,CaHVA: +3.4 mV; Vslom*,CaHVA: × 1.12; Voffh*,CaHVA: −5.3 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .601 | |
| Voffm*,CaHVA: −10.6 mV; Vslom*,CaHVA: × .8; Voffh*,CaHVA: +1.2 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .100 | |
| Voffm*,CaHVA: +3.4 mV; Vslom*,CaHVA: × .8; Voffh*,CaHVA: +1.2 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .645 | |
| Voffm*,CaHVA: −10.6 mV; Vslom*,CaHVA: × 1.12; Voffh*,CaHVA: +1.2 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = .116 | |
| Voffm*,CaHVA: +3.4 mV; Vslom*,CaHVA: × 1.12; Voffh*,CaHVA: +1.2 mV; Vsloh*,CaHVA: × .66; τh*,CaHVA: × .72 | c = 1.117 | |
| CACNA1D | Voffm*,CaHVA: +6.6 mV; Vslom*,CaHVA: × .75; τh*,CaHVA: × .5 | c = .104 |
| Voffm*,CaHVA: +6.6 mV; Vslom*,CaHVA: × 1.19; τh*,CaHVA: × .5 | c = .068 | |
| Voffm*,CaHVA: +6.6 mV; Vslom*,CaHVA: × .75; τh*,CaHVA: × 1.12 | c = .115b | |
| Voffm*,CaHVA: +6.6 mV; Vslom*,CaHVA: × 1.19; τh*,CaHVA: × 1.12 | c = .072 | |
| CACNA1I | Voffma,CaLVA: +1.3 mV; Voffha,CaLVA: +1.6 mV; τm*,CaLVA: × .87; τh*,CaLVA: × .8 | c ≥ 2.000 |
| Voffma,CaLVA: +1.3 mV; Voffha,CaLVA: +1.6 mV; τm*,CaLVA: × 1.45; τh*,CaLVA: × .8 | c ≥ 2.000a,b | |
| ATP2A2 | γCaDynamics: × .6 | c = .093b |
| ATP2B2 | τdecay,CaDynamics: × 1.97 | c = .218 |
| ATP2B2 | τdecay,CaDynamics: × 1.5; cmin,CaDynamics: × 1.4 | c = .215a |
| ATP2B2 | τdecay,CaDynamics: × 4.45 | c = .099 |
| SCN1A | Voffm,Nat: −.3 mV; Voffh,Nat: +5 mV; Vslom,Nat: × 1.15; Vsloh,Nat: × 1.23 | c = .056a |
| SCN1A | Voffm,Nat: +2.8 mV; Voffh,Nat: +9.6 mV; Vslom,Nat: × .984; Vsloh,Nat: × 1.042 | c = .069 |
| SCN9A | Voffh*,Nap: +6.8 mV | c ≥ 2.000 |
| SCN9A | Voffh*,Nap: +3.5 mV; Vsloh,Nap: × .55; Voffm,Nat: −7.1 mV; Voffh,Nat: +17.0 mV; Vsloh,Nat: × .69 | c = .026 |
| SCN9A | Voffm,Nat: −9.1 mV; Voffh,Nat: +3.1 mV | c = .043 |
| SCN9A | Voffm,Nat: 27.6 mV; Voffh,Nat: +4.3 mV | c = .043 |
| KCNS3 | τm*,Kp: × 2.0; τh*,Kp: × 2.5; Vsloh,Kp: × .5 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: +5 mV; Voffh,Kp: 13 mV; Vslom,Kp: × 1.11; Vsloh,Kp: × .86; τm*,Kp: × .5; τh*,Kp: × .53 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: +1 mV; Voffh,Kp: −6 mV; Vslom,Kp: × 1.22; Vsloh,Kp: × 1.0; τm*,Kp: × .89; τh*,Kp: × 1.13 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: +6 mV; Voffh,Kp: −8 mV; Vslom,Kp: × 1.33; Vsloh,Kp: × 1.0; τm*,Kp: × .5; τh*,Kp: × .87 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: −28 mV; Voffh,Kp: −27 mV; Vslom,Kp: × 1.11; Vsloh,Kp: × .71; τm*,Kp: × 1.13; τh*,Kp: × 2.27 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: +14 mV; Voffh,Kp: −21 mV; Vslom,Kp: × 2.0; Vsloh,Kp: × 1.0; τm*,Kp: × .39; τh*,Kp: × 1.2 | c ≥ 2.000 |
| KCNB1 | Voffm,Kp: −13 mV; Voffh,Kp: −13 mV; Vslom,Kp: × 1.33; Vsloh,Kp: × .71; τm*,Kp: × .95; τh*,Kp: × 5.13 | c ≥ 2.000 |
| KCNN3 | Coff,SK: × .86; Cslo,SK: × 1.24 | c = 1.715a,b |
| HCN1 | Voffm*,Ih: −26.5 mV; Vslom*,Ih: × .64 | c = .296 |
The variants are ordered as in Table 1, but the variants where several combinations of parameter range end points were considered are listed as separate variants (Supplement 1).
CaHVA, high-voltage activated Ca2+; CaLVA, low-voltage activated Ca2+; Ih, nonspecific cation current; Kp, slow inactivating K+; Nap, persistent Na+; Nat, fast inactivating Na+; SK, small-conductance Ca2+-activated K+.
b
The variants were used in Figure S3 in Supplement 1.
c
The variant was used in Figure 1.