Table 1.
Potentially pathogenic and causative SNVs detected, excluding RTT genes.
| Num. Patients | Gene | OMIM number | Transcript | Type of seq. Change | cDNAchange | Proteinchange | dbSNP | Mutation taster, SIFT, PROVEAN, PolyPhen-2 scores |
|---|---|---|---|---|---|---|---|---|
| Potentially pathogenic mutation detected by HCP | ||||||||
| 2 | STXBP1 | 602926 | NM_003165 | Missense | c.874C>T | p.Arg292Cys | — | Disease causing, 0, 0.996, −7.58 |
| 2 | STXBP1 | 602926 | NM_003165 | Missense | c.875G>A | p.Arg292His | rs796053361 | Disease causing, 0, 1, −4.74 |
| 1 | KCNQ2 | 602235 | NM_172107 | Missense | c.593G>A | p.Arg198Gln | rs796052621 | Disease causing, 0, 1, −3.58 |
| 1 | KCNQ2 | 602235 | NM_172107 | Missense | c.637C>T | p.Arg213Trp | rs118192203 | Disease causing, 0, 1, −7.19 |
| 1 | SLC2A1 | 138140 | NM_006516 | Missense | c.805C>T | p.Arg269Cys | rs200247956 | Disease causing, 0, 1, −7.79 |
| 1 | STXBP1 | 602926 | NM_003165 | Missense | c.1216C>T | p.Arg406Cys | rs796053367 | Disease causing, 0, 1, −7.86 |
| 1 | STXBP1 | 602926 | NM_003165 | In-frame deletion | c.124_126delTCC | p.Ser42del | — | Disease causing, NA, NA, −10.71 |
| 1 | STXBP1 | 602926 | NM_003165 | Splicing variant | c.326-3C>G | Miss-splicing | — | NA, NA, NA, NA |
| 1 | STXBP1 | 602926 | NM_003165 | Missense | c.704G>A | p.Arg235Gln | — | Disease causing, 0, 1, −3.79 |
| 1 | TCF4 | 602272 | NM_001243236 | In-frame indel | c.1169_1175delTAGAAAGinsAAA | p.Leu390Ter | — | Disease causing, NA, NA, NA |
| 1 | TCF4 | 602272 | NM_001243236 | Missense | c.1733G>A | p.Arg578His | rs121909123 | Disease causing, 0, 1, −4.73 |
| 1 | TCF4 | 602272 | NM_001243236 | Nonsense | c.1774C>T | p.Gln592Ter | — | Disease causing, NA, NA, NA |
| 1 | TCF4 | 602272 | NM_001243236 | Frameshift deletion | c.514_517delAAAG | p.Lys172PhefsTer61 | rs398123561 | Disease causing, NA, NA, NA |
| Potentially pathogenic mutation detected by TSO | ||||||||
| 1 | MEF2C | 600662 | NM_001193347 | Missense | c.48C>G | p.Asn16Lys | — | Disease causing, 0.013, 0.995, −5.35 |
| 1 | MEF2C | 600662 | NM_001193347 | Frameshift deletion | c.989_990delGT | p.Gly330AspfsTer7 | — | Disease causing, NA, NA, NA |
| 1 | SCN2A | 182390 | NM_001040142 | Missense | c.3631G>A | p.Glu1211Lys | rs387906684 | Disease causing, 0, 0.995, −3.82 |
| 1 | SCN2A | 182390 | NM_001040142 | Missense | c.5317G>A | p.Ala1773Thr | — | Disease causing, 0, 1, −3.68 |
| 1 | SYNGAP1 | 603384 | NM_006772 | Frameshift deletion | c.2019delA | p.Thr674ProfsTer36 | — | Disease causing, NA, NA, NA |
| 1 | SYNGAP1 | 603384 | NM_006772 | Frameshift deletion | c.1782delC | p.Leu595CysfsTer55 | rs587780470 | Disease causing, NA, NA, NA |
| Potentially pathogenic mutation detected by WES | ||||||||
| 1 | CACNA1I | 608230 | NM_021096 | Missense | c.4435C>T | p.Leu1479Phe | — | Disease causing, 0.397, 0.756, −1.53 |
| 1 | CHRNA5 | 118505 | NM_000745 | Missense | c.748C>A | p.Pro250Thr | — | Disease causing, 0.301, 1, −6.07 |
| 1 | GABBR2 | 607340 | NM_005458 | Missense | c.1699G>A | p.Ala567Thr | — | Disease causing, 0.002, 0.999, −3.48 |
| 1 | GRIN2B | 138252 | NM_000834 | Missense | c.1657C>A | p.Pro553Thr | — | Disease causing, 0.001, 0.975, −6.8 |
| 1 | HCN1 | 602780 | NM_021072 | Missense | c.1159G>T | p.Ala387Ser | — | Disease causing, 0.002, 0.767, −2.76 |
Variant effect predictors web tools used: Mutation taster (http://www.mutationtaster.org/); SIFT-PROVEAN, SIFT scores ranged from 0–1, where 0 is predicted to be most damaging and Protein Variation Effect Analyzer (PROVEAN) score ≤−2.5, the protein variant is predicted to have a “deleterious” effect, while if the PROVEAN score is >−2.5, the variant is predicted to have a “neutral” effect (http://provean.jcvi.org/genome_submit_2.php); and Polyphen-2, ranged from 0–1, where 1 is most likely to be damaging (http://genetics.bwh.harvard.edu/pph2/).