Table 3.
Statistical Analysis of clinical and genetic characteristics of children with Dravet syndrome and those without Dravet syndrome
| Case | Nucleotide variation | Amino acid changes | Variant type | Inheritance | Genetic pattern | ACMG | DS | Mutation Taster | PolyPhen-2 | PROVEAN | Functional Prediction | Reported |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | c.4361 A > G | p.Glu1454Gly | Missense | De novo | AD | P | Yes | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.187) | LOF | No |
| 2 | c.1178G > C | p.Arg393Pro | Missense | De novo | AD | P | Yes | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.875) | LOF | Yes |
| 3 | c.2131 C > T | p.Gln711Ter,1299 | Nonsense | De novo | AD | P | Yes | - | - | - | - | Yes |
| 4 | c.3800T > C | p.Met1267Thr | Missense | Paternal | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-5.661) | LOF | No |
| 5 | c.4339- 1(IVS22) G > A | — | Splicing | De novo | AD | P | Yes | - | - | - | - | Yes |
| 6 | c.2575 C > T | p.Arg859Cys | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-7.346) | LOF | Yes |
| 7 | c.4268T > C | p. Leu1423Pro | Missense | Unknown | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.672) | LOF | No |
| 8 | c.5522T > C | p.Leu1841Pro | Missense | De novo | AD | LP | No | Disease causing (0.99) | Probably damaging(0.913) | Deleterious(-7.348) | LOF | Yes |
| 9 | c.5020G > C | p.Gly1674Arg | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.963) | LOF | Yes |
| 10 | c.631 A > G | p.Asn211Asp | Missense | De novo | AD | P | No | Disease causing (0.99) | Possibly damaging(0.743) | Deleterious(-4.739) | GOF | No |
| 11 | c.5641G > A | p.Glu1881Lys | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(0.995) | Deleterious(-3.648) | No functional effect | Yes |
| 12 | c.3429(exon18)_c.3429 + 1(IVS18)insCTT | p.Lys1144insLeu | Insertion | De novo | AD | LP | No | - | - | - | - | No |
| 13 | c.1702 C > T | p.Arg568Ter,1442 | Nonsense | De novo | AD | P | Yes | - | - | - | - | Yes |
| 14 | c.3733 C > T | p.Arg1245Ter,765 | Nonsense | De novo | AD | P | Yes | - | - | - | - | Yes |
| 15 | c.724 C > G | p.Gln242Glu | Missense | Maternal | AD | LP | No | Disease causing (0.99) | Probably damaging(0.998) | Deleterious(-2.931) | GOF | No |
| 16 | c.2815_c.2816 insTTCC | p.His939Leufs*59 | Frameshift | De novo | AD | P | No | - | - | - | - | No |
| 17 | c.2589 + 3(IVS14)A > T | — | Splicing | De novo | AD | P | Yes | - | - | - | - | Yes |
| 18 | c.4699delG | p.Glu1567Asnfs*3 | Frameshift | De novo | AD | P | Yes | - | - | - | - | No |
| 19 | c.5115_c.5116 insC | p.Asn1706Glnfs*3 | Frameshift | De novo | AD | P | No | - | - | - | - | No |
| 20 | c.5725 A > G | p.Thr1909Ala | Missense | De novo | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-4.602) | Unreliable | Yes |
| 21 | c.1655delC | p.Pro552fs*6 | Frameshift | De novo | AD | P | No | - | - | - | - | No |
| 22 | c.3818 C > T | p.Ala1273Val | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-3.737) | Unreliable | Yes |
| 23 | c.2435 C > G | p.Thr812Arg | Missense | Maternal | AD | LP | Yes | Disease causing (0.99) | Possibly damaging(0.703) | Deleterious(-4.944) | LOF | Yes |
| 24 | c.829T > G | p.Cys277Gly | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-11.647) | Unreliable | Yes |
| 25 | c.5765T > C | p.Ile1922Thr | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-4.409) | Unreliable | Yes |
| 26 | c.2134 C > T | p.Arg712Ter,1298 | Nonsense | De novo | AD | P | No | - | - | - | - | Yes |
| 27 | c.1010G > A | p.Gly337Glu | Missense | De novo | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-7.639) | LOF | Yes |
| 28 | c.268T > G | p.Phe90Val | Missense | De novo | AD | LP | No | Disease causing (0.99) | Probably damaging(0.992) | Deleterious(-6.003) | LOF | No |
| 29 | c.5111T > C | p.Met1704Thr | Missense | De novo | AD | LP | Yes | Disease causing (0.99) | Probably damaging(0.999) | Deleterious(-5.090) | LOF | Yes |
| 30 | c.821G > C | p.Arg274Thr | Missense | Paternal | AD | VUS | No | Disease causing (0.99) | Probably damaging(0.982) | Deleterious(-5.514) | LOF | No |
| 31 | c.2378 C > T | p.Thr793Met | Missense | Paternal | AD | VUS | No | Disease causing (0.99) | Probably damaging(0.995) | Deleterious(-5.365) | LOF | Yes |
| 32 | c.4063 C > T | p.Leu1355Pro | Missense | Paternal | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-3.085) | LOF | Yes |
| 33 | c.2537 A > G | p.Glu846Gly | Missense | De novo | AD | LP | No | Disease causing (0.99) | Possibly damaging(0.762) | Deleterious(-6.429) | Unreliable | Yes |
| 34 | c.5354T > A | p.Ile1785Asn | Missense | De novo | AD | LP | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.442) | LOF | No |
| 35 | c.4906 C > T | p.Arg1636X | Nonsense | De novo | AD | P | No | - | - | - | - | No |
| 36 | c.949T > A | p.Tyr317Asn | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.899) | No functional effect | No |
| 37 | c.2103G > T | p.Met701Ile | Missense | Maternal | AD | VUS | No | Disease causing (0.99) | Benign(0.008) | Neutral(-2.281) | No functional effect | No |
| 38 | c.374delT + c.365_367delTTA | p.Leu125Trpfs*9+(p.122_123delIKinsK) | Frameshift | de novo | AD | P | Yes | - | - | - | - | No |
| 39 | c.3724_3725del | p.Ile1242fs | Frameshift | De novo | AD | P | Yes | - | - | - | - | No |
| 40 | c.3880-2(IVS22)A > G | — | Splicing | De novo | AD | P | No | - | - | - | - | Yes |
| 41 | c.4958 C > A | p.Ala1653Glu | Missense | De novo | AD | P | Yes | Disease causing (0.99) | Probably damaging(1) | Deleterious(-4.355) | GOF | Yes |
| 42 | c.4510 C > T | p.Gln1504* | Nonsense | De novo | AD | P | Yes | - | - | - | - | No |
| 43 | c.2416- 1(IVS16)G > T | — | Splicing | De novo | AD | P | Yes | - | - | - | - | No |
| 44 | c.1970 C > T | p.Pro657Leu | Missense | Maternal | AD | VUS | No | Disease causing (0.99) | Benign(0.051) | Deleterious(-3.445) | Unreliable | Yes |
| 45 | c.2064_c.2074delA ATGAGAAAGA | p.Met689fs*36 | Frameshift | De novo | AD | P | No | - | - | - | - | No |
| 46 | c.1121 C > T | p.Ser374Phe | Missense | Paternal | AD | LP | No | Disease causing (0.99) | Probably damaging(0.999) | Deleterious(-4.550) | LOF | Yes |
| 47 | loss1(exon:4–19) | 37,575 bp | Deletion | De novo | AD | P | No | - | - | - | - | No |
| 48 | c.2729 A > G | p.Gln910Arg | Missense | De novo | AD | LP | Yes | Disease causing (0.99) | Probably damaging(0.974) | Deleterious(-3.870) | GOF | Yes |
| 49 | c.2852 A > G | p.Glu951Gly | Missense | De novo | AD | P | No | Disease causing (0.99) | Probably damaging(1) | Deleterious(-6.773) | LOF | No |
| 50 | c.2462 C > T | p.Ala821Val | Missense | Maternal | AD | VUS | No | Disease causing (0.99) | Possibly damaging(0.683) | Deleterious(-3.743) | No functional effect | No |
Note: P, pathogenic; LP, likely pathogenic; VUS, uncertain significance