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. 2023 Jul 20;6(7):e2324380. doi: 10.1001/jamanetworkopen.2023.24380

Table 2. Diagnostic Genetic SNVs and CNVs and Their Associated Phenotypes, From a Cohort of 522 Patients With Unexplained Pediatric Epilepsya.

Participant ID Gene or coordinate Variant or size/type of CNV Inheritance ACMG/AMP for SNVs or syndrome/involved genes for CNVs Age at seizure onset Sex Epilepsy type Syndrome
SNVs
1 ANKRD11 c.3039_3045del, p.Asp1013GlufsTer303 De novo P 14 y Female Combined NR
2 c.7535G>A, p.Arg2512Gln Unknown P 1 y Female DEE LGS
3 ARHGEF9 c.1285del, p.Glu429LysfsTer19 Unknown LP 4 mo Female DEE NR
4 ARID1B c.3586C>T, p.Gln1196Ter De novo P 8 y Female NAFE NR
5 ATN1 c.3193C>T, p.Gln1065Ter De novo VUS 10 y Male GGE NR
6 BCL11A c.198C>G, p.His66Gln Unknown LP 2 y Female GGE EEM
7 BRAF c.770A>G, p.Gln257Arg De novo P 1 y 6 mo Male DEE NR
8 BRAT1 c.1925C>A, p.Ala642Glu Paternal LP 6 wk Female DEE NR
c.294dupA, p.Leu99ThrfsTer92 Maternal P
9 BRWD3 c.4080+1G>A Maternal LP 2 y Male NAFE NR
10 CACNA1A c.601C>T, p.Arg201Trp Unknown LP 4 y Female IGE CAE
11 CACNA1G c.3568C>T, p.Arg1190Ter De novo VUS 5 y Female IGE CAE
12 CHD2 c.2876+3_2876+6delAAGT De novo LP 1 y Female DEE NR
13 c.3895_3896insC, p.Val1299AlafsTer5 Unknown P 1 y 10 mo Male DEE NR
14 CLN8 c.784G>A, p.Asp262Asn Unknown LP 5 y 6 mo Female DEE NR
c.610C>T, p.Arg204Cys Maternal P
15 CREBBP c.5315T>A, p.Ile1772Asn Unknown LP Infantile Male DEE NR
16 CSNK2A1 c.921T>G, p.Tyr307Ter De novo LP 9 m Female DEE NR
17 CSNK2B c.557+1G>A Unknown LP 2 m Male DEE NR
18 CYFIP2 c.2542A>G, p.Met848Val De novo LP 4 m Male DEE IESS
19 DEPDC5 c.363+1G>A Paternal LP 3 y Male NAFE NR
20 c.667A>G, p.Arg223Gly Maternal VUS 8 y Male NAFE NR
21 c.1459C>T, p.Arg487Ter Unknown P 10 y Female GGE NR
22 DYNC1H1 c.5864G>T, p.Gly1955Val De novo LP 2 mo Male DEE IESS
23 EEF1A2 c.364G>A, p.Glu122Lys De novo P Infantile Male DEE NR
24 FRRS1L c.737_739del, p.Gly246del Unknown P 11 mo Female DEE NR
25 FOXP1 c.-448G>C Unknown VUS 4 y Male DEE LGS
26 GABRA5 c.902C>T, p.Thr301Met De novo LP 11 y Female Combined NR
27 GABRG2 c.1087C>T, p.Arg363Trp Unknown LP 1 y Male GGE NR
28 c.542C>A, p.Thr181Asn Maternal LP 7 y Female NAFE NR
29 GFAP c.882C>A, p.Cys294Ter Unknown VUS 2 y Male GGE NR
30 GPHN c.1471A>T, p.Arg491Ter Unknown P 1 y Male GGE NR
31 GRIA3 c.1580C>A, p.Ser527Arg Maternal VUS 1 y 6 mo Male GGE NR
32 GRIN2A c.1122+1G>C Unknown LP 3 y Male NAFE NR
33 GRIN2B c.1843A>T, p.Asn615Tyr De novo P 2 mo Female DEE IESS
34 KCNA2 c.217C>T, p.Arg73Ter Unknown LP 9 y Male Combined NR
35 KCNMA1 c.1918C>T, p.Arg640Ter Paternal LP 8 y Female Combined NR
36 c.3199A>G, p.Lys1067Glu De novo LP 14 y Female IGE JME
37 KCNQ2 c.365C>T, p.Ser122Leu De novo P 3 d Female DEE NR
38 KCNQ3 c.688C>T, p.Arg230Cys De novo P 5 y Female DEE NR
39 KDM4B c.719G>A, p.Arg240Gln De novo LP 1 y 6 mo Male DEE NR
40 KDM6B c.40C>G, p.Arg14Gly De novo VUS 4 mo Female GGE NR
41 KMT2E c.1097_1116del20, p.Glu366ValfsTer4 De novo P 4 y Female IGE CAE
42 LGI1 c.757G>A, p.Ala253Thr Maternal VUS 4 y 6 mo Male NAFE SELECTS
43 MECP2 c.1200_1243del, p.Pro401Ter De novo P 3 y Female NAFE SHE
44 MTR c.2411T>C, p.Ile804Thr Paternal VUS 5 mo Female DEE IESS
c.2472A>T, p.Ala824= Maternal VUS
45 NBEA c.4702dup, p.Val1568GlyfsTer14 De novo P 1 y 6 mo Male DEE EMATS
46 NEXMIF c.846_849delTGTC, p.V283tfsX20 De novo mosaic P 5 y Female GGE NR
47 NPRL2 c.323_339+19del Paternal P 3 mo Male NAFE IESS
48 OTUD6B c.433C>T, p.Arg145Ter Both P 9 mo Male DEE IESS
49 PCDH19 c.811_825del, p.Gly271_Tyr275del De novo LP 9 mo Female DEE NR
50 c.1335C>A, p.Asp445Glu Maternal LP 6 mo Female DEE NR
51 POLR2A c.3281C>T, p.Ser1094Phe De novo LP 2 y Male DEE NR
52 PGAP2 c.823A>G, p.Met275Val Unknown LP 5 mo Male DEE IESS
c.1040C>T, p.Ala347Val Maternal LP
53 POLG c.1760C>T/c.752C>T, p.Pro587Leu/p.Thr251Ile Maternal P 5 y Male GGE NR
c.1703G>C, p.Gly568Ala Paternal VUS
54 PPP2R5D c.592G>A, p.Glu198Lys Unknown P 2 y Male DEE NR
55 PRRT2 c.870delT, p.Tyr290Ter De novo P 5 mo Female NAFE SELIE
56 c.649dup, p.Arg217ProfsTer8 Paternal P 3 mo Female NAFE NR
57 c.649dup, p.Arg217ProfsTer8 Maternal P 5 mo Male GGE SELIE
58 RORA c.680del, p.Thr227ArgfsTer80 De novo P 6 y Male Combined NR
59 SCN1A c.5066T>C, p.Met1689Thr De novo LP 3 y Male Combined NR
60 c.5495C>A, p.Ala1832Glu Maternal mosaic P 6 mo Male DEE DS
61 c.3429G>C, p.Glu1143Asp De novo LP 6 mo Male DEE DS
62 c.664C>T, p.Arg222Ter Maternal mosaic P 9 mo Male DEE DS
63 c.4634T>G, p.Ile1545Arg De novo P 3 mo Male GGE NR
64 c.2955T>G, p.Asn985Lys Unknown LP 6 mo Female NAFE NR
65 c.332T>A, p.Leu111Ter De novo mosaic P 11 mo Male NAFE GEFS+
66 c.4057G>A, p.Val1353Ile Unknown P 6 mo Male DEE NR
67 c.5606T>C, p.Phe1869Ser Maternal VUS 2 y Male GGE NR
68 SCN1B c.363C>G, p.Cys121Trp Maternal LP 1 y 6 mo Female NAFE NR
69 c.1A>C, p.Met1? Paternal LP 2 y Female GGE NR
70 SCN8A c.3955G>T, p.Ala1319Ser De novo P 3 wk Male DEE NR
71 SETD1A c.4268A>G, p.Gln1423Arg De novo LP 11 mo Female DEE HHE
72 SETD1B c.5726T>C, p.Ile1909Thr De novo LP 5 y Female IGE CAE
73 SHANK3 c.3949dupG, p.Val1317GlyfsX28 De novo P 8 y Female DEE NR
74 SLC12A5 c.1052A>G, p.Asn351Ser Both LP 3 m Female DEE EIMFS
75 SON c.6888T>G, p.Asp2296Glu De novo LP 8 y Male DEE NR
76 SPATA5 c.2045C>T, p.Ala682Val Maternal LP 3.5 y Male DEE NR
c.1883A>G, p.Asp628Gly Paternal LP
77 SPTAN1 c.6589_6594dupGAGCT, p.Glu2197_Leu2198dup De novo P 2 y Male DEE NR
78 SRCAP c.8919del, p.Leu2975Ter Unknown P 5 y Female GGE NR
79 STAG1 c.1145C>T, p.Thr382Ile De novo VUS 1 y 3 mo Female NAFE NR
80 STXBP1 c.1652G>A, p.Arg551His Unknown P 1 m Female DEE IESS
81 c.847G>A, p.Glu283Lys Unknown P 1 y 6 mo Male NAFE NR
82 SYNGAP1 c.403C>T, p.Arg135Ter De novo P 3 y Female DEE NR
83 c.1630C>T, p.Arg544Ter Unknown P 2 y Male DEE NR
84 TANC2 c.2326G>T, p.Glu776Ter De novo P 8 mo Female DEE IESS, LGS
85 TCF4 c.1486+5delG De novo LP 11 y Female DEE NR
86 TRIT1 c.967C>T, p.Arg323Trp Both LP 1 y 6 mo Female DEE NR
87 UBA5 c.829G>A, p.Gly277Ser Paternal LP 1 y 11 mo Male NAFE NR
c.1111G>A, p.Ala371Thr Maternal P
88 WDR26 c.706C>G, p.Leu236Val Unknown VUS 3 y Male DEE NR
89 ZEB2 c.3135C>G, p.His1045Gln Unknown VUS 2 y 6 mo Female GGE NR
CNVs
90 chr2:166847505-167334456 487 kb deletion De novo SCN1A 1 y Male Combined NR
91 chr3:11058648-11060634 2 kb deletion Unknown27 SLC6A1 1 y 10 mo Female GGE NR
92 chr16:138446-140150 1.7 kb deletion Unknown NPRL3 4 mo Male NAFE IESS
93 chr22:32121274-32302733 181 kb deletion Maternal DEPDC5 6 y Male NAFE NR
94 chr22:32193336-32194893 1.5 kb deletion Maternal DEPDC5 3 y Male NAFE NR
95 chr1:146630894-147415874 785 kb deletion Paternal 1q21.1 recurrent microdeletion 5 y Female IGE CAE
96 chr15:30896079-32404350 1.5 Mb deletion De novo 15q13.3 recurrent microdeletion 6 y Female GGE EMA
97 chr16:29674800-30199626 525 kb duplication De novo 16p11.2 recurrent microduplication 8 mo Male NAFE NR
98 chr16:21964495-22385880 421 kb deletion Maternal 16p12.1 recurrent microdeletion 4 y Male GGE NR
99 chr16:14960162-16297720 1.3 Mb deletion Maternal 16p13.11 recurrent microdeletion 14 y Male NAFE NR
100 chr22:18893638-21386351 2.5 Mb deletion De novo 22q11 deletion syndrome 6 y Female GGE NR

Abbreviations: ACMG/AMP, American College of Medical Genetics and Genomics/Association for Molecular Pathology; ASM, antiseizure medication; CAE, childhood absence epilepsy; CNV, copy number variant; DEE, developmental and epileptic encephalopathy; DS, Dravet syndrome; EEM, epilepsy with eyelid myoclonia; EIMFS, epilepsy of infancy with migrating focal seizures; EMA, epilepsy with myoclonic absences; EMATS, epilepsy with myoclonic-atonic seizures; GEFS+, generalized epilepsy with febrile seizure plus; GGE, genetic generalized epilepsy; HHE, hemiconvulsion-hemiplegia epilepsy syndrome; ID, identification number; IESS, infantile epileptic spasm syndrome; IGE, idiopathic generalized epilepsy; JME, juvenile myoclonic epilepsy; LGS, Lennox-Gastaut syndrome; LP, likely pathogenic; NAFE, nonacquired focal epilepsy; NR, not reported; P, pathogenic; SELECTS, self-limited epilepsy with centrotemporal spikes; SELIE, self-limited infantile epilepsy; SHE, sleep-related hypermotor epilepsy; SNV, single nucleotide variant; VUS, variants of uncertain significance.

a

Gene, variant, and ACMG/AMP classification are given for SNVs. Coordinate, size/type of CNV, and syndrome or genes involved are given for CNVs.