Table 2.
Pathogenicity analysis of monogenic variants in epilepsy with photosensitivity.
| Patient | Gene | Variant | Genome build (GRCh37) | Nucleotide change | Inheritance | EXAC allele frequency (v1.0) | Allele frequency in updated gnom AD (v2.1.1 and v3.1.1) | Reported in the Clinvar | ACMG classification |
|---|---|---|---|---|---|---|---|---|---|
| 1 | TPP1 (NM_000391.4) |
p.Ser475Leu | Chr11:6636403G>A | c.1424C>T | Heterozygous | <0.01% | <0.01% | Yes | P |
| 1 | TPP1 | p.Ser408del | Chr11:6636715_6636717delACT | c.1222_1224delAGT | Heterozygous | 0 | <0.01% | No | LP |
| 2 | TPP1 | p.Gly172Aspfs*11 | Chr11:6638378_6638378delC | c.515delG | Homozygous | 0 | 0 | No | P |
| 3 | TPP1 | p.Glu59Aspfs*21 | Chr11:6640056_6640059delTCTT | c.177_180delAAGA | Homozygous | 0 | 0 | No | P |
| 4 | KCTD7 (NM_153033.5) |
p.Arg153His | Chr7:66103383G>A | c.458G>A | Heterozygous | <0.01% | <0.01% | Yes | P |
| 4 | KCTD7 | p.Ala178Val | Chr7:66103882C>T | c.533C>T | Heterozygous | <0.01% | <0.01% | Yes | P |
| 5 | MFSD8 (NM_152778) |
p.Phe186Cys | Chr4:128861149A>C | c.557T>G | Heterozygous | 0 | 0 | No | LP |
| 5 | MFSD8 | - | Chr4:128841992C>T | c.1351-1G>A | Heterozygous | 0 | <0.01% | No | P |
| 6 | KCNC1 (NM_001112741.2) |
p.Arg320His | Chr11:17793600G>A | c.959G>A | De novo | 0 | 0 | Yes | P |
| 7 | GBA (NM_000157.4) |
p.Asn227Ser | Chr1:155208006T>C | c.680A>G | Heterozygous | <0.01% | <0.01% | Yes | P |
| 7 | GBA | p.Leu483Pro | Chr1:155205043A>G | c.1448T>C | Heterozygous | <0.01% | <0.5% | Yes | P |
| 11 | CHD2 (NM_001271.4) |
p.Val882Phe | Chr15: 93521530G>T | c.2644G>T | De novo | 0 | 0 | No | LP |
| 12 | CHD2 | p.Lys1351Serfs*11 | Chr15:93543785_93543786delAA | c.4051_4052delAA | De novo | 0 | 0 | No | P |
| 13 | CHD2 | p.Lys1426Asnfs*51 | Chr15:93545547delG | c.4278delG | De novo | 0 | 0 | No | P |
| 14 | CHD2 | p.T573i | Chr15:93496803G>A | c.1719G>A | De novo | 0 | 0 | Yes | P |
| 15 | CHD2 | p.Arg1152Trp | Chr15:93534746C>T | c.3454C>T | De novo | 0 | 0 | Yes | P |
| 16 | CHD2 | p.Ser1386Lysfs*23 | Chr15:93545425_93545426insA | c.4156_4157insA | De novo | 0 | 0 | No | P |
| 17 | SYNGAP1 (NM_006772.3) |
p.Gln1021* | Chr6:33411390C>T | c.3061C>T | De novo | 0 | 0 | No | P |
| 18 | SNGAP1 | p.Gln662* | Chr6:33409020C>T | c.1984C>T | De novo | 0 | 0 | No | P |
| 19 | SYNGAP1 | p.Tyr505Serfs*22 | Chr6:33406323_33406323delA | c.1514delA | De novo | 0 | 0 | No | P |
| 20 | GABRA1 (NM_001127644.2) |
p.Leu215Pro | Chr5:161309648T>C | c.644T>C | De novo | 0 | 0 | No | LP |
| 21 | GABRA1 | p.Ser76Arg | Chr5:161292676T>G | c.228T>G | De novo | 0 | 0 | No | LP |
| 22 | GABRG2 (NM_198904.4) |
p.Leu81pro | Chr5:161520968T>C | c.242T>C | De novo | 0 | 0 | No | LP |
| 23 | CACNA1A (NM_00112722.2.) |
p.Gln680Argfs*10000 | Chr19:13414645_13414646delCT | c.2039_2040delAG | De novo | 0 | 0 | Yes | P |
| 24 | KCNMA1 (NM_002247.3) |
p.Asn995Ser | Chr10:78651467T>C | c.2984A>G | De novo | 0 | 0 | No | P |
| 25 | SLC2A1 (NM_006516.4) |
p.Arg400His | Chr1:43393355C>T | c.1199G>A | De novo | 0 | 0 | Yes | P |
| 26 | FLNA (NM_001110556.2) |
p.Glu415Lys | Chr23:153594578C>T | c.1243G>A | His mother | <0.01% | <0.01% | No | LP |
| 27 | SZT2 (NM_015284) |
p.Val1902Ala | Chr1:43900128T>C | c.5705T>C | Heterozygous | 0 | <0.01% | No | LP |
| 27 | SZT2 | p.Lys963Glu | Chr1:43891578A>G | c.2887A>G | Heterozygous | <0.01% | <0.01% | Yes | P |
| 28 | SCN1A (NM_001165963.4) |
p.Pro1519Thrfs*18 | Chr2:166852549_166852550insT | c.4554dupA | De novo | 0 | 0 | No | P |
| 29 | SCN1A | p.Met400Aspfs*49 | Chr2:166903459_166903460delTG | c.1197_1198delCA | De novo | 0 | 0 | No | P |
| 30 | SCN1A | p.Tyr1279Phefs*14 | Chr2:166868661_166868662delAT | c.3836_3837delAT | De novo | 0 | 0 | No | P |
| 31 | SCN1A | p.Val944Ala | Chr2:166894401A>G | c.2831T>C | De novo | 0 | 0 | Yes | P |
| 32 | SCN1A | p.Thr363Ile | Chr2:166904219G>A | c.1088C>T | De novo | 0 | 0 | No | LP |
| 33 | SCN1A | p.Asn301Metfs*5 | Chr2:166908291_166908291delT | c.902delA | De novo | 0 | 0 | No | P |
| 34 | SCN1A | p.Cys1588Gly | Chr2:166850746A>C | c.4762T>G | De novo | 0 | 0 | No | LP |