Table 1:

Clinical summary table indicating demographics, variant details with American College of Medical Genetics and Genomics classifications predicted by Franklin/Varsome, allele frequencies, and phenotype summaries for each individual in the study.

ID	Sex, Age range (years)	DENND5A variant(s)	Predicted ACMG classification	Allele frequency	Other gene variants	Seizures (drag resistant)	Seizure type(s)	Medications that controlled, [did not affect], or (worsened) seizures	Microcephaly (OFC %ile)	6FRUHV			Developmental outcome
										Neuro	Motor	Communication
										1	M, 6-10	p.R698W p.N1017S		VUS VUS	2.78 x 10−5 1.59 x 10−5	CNOT3 (VUS)	Y (N)	Unclassified (described as infantile spasms and focal left hemisphere involvement)	Vigabatrin, levetiracetam, [ACTH]	N (97)	2	10	2	Moderate ID
2	F, 6-10	c.1453A>G / p.K485E c.2129G>A / p.R710H	LB/VUS LB/VUS	7.08 X 10−4 5.17 x 10−5		Y (Y)	Generalized epileptic spasms, generalized atonic	[prednisolone, vigabatrin, clobazam lamotrigine, leveliracetam, felbamale rufinamide, VNS therapy]	Y (<3)	4	0	4	Profound ID
3	M, 16-20	c.611_612insG / p.K20SX	LP	N/A	-	Y (Y)	Generalized tonic-donic	Valproic acid, lamotrigine, ativan, clobazam	Y (UK, −8.9 SD)	9	6	6	Profound ID
422	F, 6-10	c.1622A>G / p.D541G	VUS	N/A	-	Y (Y)	Focal impaired awareness tdnic-clonic; focal to bilateral tonic-clonic	Levetiracelam carbamazepine, clonazepam, topiramate, vigabatrin [(phenobarbital)]	Y (<3)	3	3	0	GDD (assessed age 1-5 y)
522	F, deceased 6-10	c.3811del / p.Q1271Rfs*67	VUS/P	N/A	-	Y (Y)	Focal aware tonic-clonic; focal to bilateral tonic-clonic	Phenobarbital, levetiracetam, [carbamazepine]	Y (<3)	10	0	1	GDD (assessed age 1-5 y]
7	F, 11-15	c.1363T>C / p.S455P c.3733G>A / p.A1245T	vus LB/VUS	N/A 7.96 x 10−6	PEX1 (P)	Y (N)	Focal impaired awareness automatism, clonic, and atonic; generalized tonic-clonic	No medication	N (51)	4	9	4	Severe ID
8	M, 11-15	c.1453A>G / p.K485E c.3475C>T / p.R1159W	LB/VUS VUS	7.08 x 10−4 9.20 x 10−5	HERC2 (VUS), MYBPC3 (P)	N	N/A	N/A	N (90)	1	10	9	No GDD/ID
9	F, deceased 1-5	c.950-20_950-17delTTTT c.3233G>A / p.R1078Q	LB LB/VUS	4.06 x 10−5 2.62 x 10−4	TBCK (LB/VUS)	Y (Y)	Focal behavior arrest; unclassified (described as infantile spasms, myoclonic, and atonic seizures)	Topiramate, ACTH, [vigabatrin, diazepam, dexamethasone pyridoxine, CBD oil, clobazam, sabril, prednisone, levocamitine]	N (14)	4	1	3	Severe ID
10	F, 11-15	c.2547del / p.K850Sfs*11	P	N/A	-	Y (UK)	Generalized tonic-donic	UK	Y (<1)	5	9	7	Severe ID
12	M, 1-5	c.2314C>T / p.R772X c.3013T>A / p.L1005M	P VUS	3.19 x 10−5 N/A	CNV: 607 kb gain 6q25.3	Y (N)	UK; seizure associated with hypoglycemia	Phenobarbital, levetiracetam, CBD oil	Y (<1)	2	2	5	GDD
14	M, 1-5	c.2180dupG / p.S728fs*34	P	N/A	-	Y (Y)	Focal tonic and myoclonic; generalized absence	Levetiracetam, valproic acid	Y (<1)	10	0	1	GDD
1521	F, 11-15	c.517_518delGA / p.D173Qfs*8	P	N/A	-	Y (Y)	Focal impaired awareness tonic and myoclonic; focal to bilateral tonic-clonic	Temporary control with lamotrigine	N (50)	7	3	3	Severe ID
1621	F, deceased	c.517_518delGA / p.D173Qfs*8	P	N/A	-	Y (Y)	Focal impaired awareness tonic and myoclonic; focal to bilateral tonic-clonic	Temporary control with lamotrigine	Y (<2)	7	2	3	Severe ID
18	F, 16-20	c.2283+1G>T c.3018dupG / p.K1007Efs*10	VUS/LP LP	N/A N/A	-	Y (Y)	focal impaired awareness clonic and tonic; focal epileptic spasms; focal to bilateral tonic-clonic focal impaired awareness behavior arrest; generalized molor onset myoclonic and tonic; unknown onset epileptic spasms; unknown onset behavior arrest	Vigabatrin, valproic acid, levetiracetam, [phenobarbital, sultiame]	Y (<1)	6	0	2	Profound ID
19	M, 6-10	c.407C>G / p.T136R c.2864C>T / p.P955L	VUS VUS	N/A 1.59 x 10−5	CACNA1C (LP/P)	N	N/A	N/A	N (50)	No imaging	9	9	Moderate ID
20	M, 1-5	Exon 1-14 dup	VUS	N/A	-	N/A	N/A	N/A	N (4)	0	7	2	GDD
21	M, 16-20	c.1549C>T / p.R517W Exon 1 del	VUS LP	7.96 x 10−6 N/A	-	Y (Y)	Focal tonic; focal impaired awareness; focal clonic; focal to bilateral tonic-clonic	Current trial: clobazam, lamotrigine, CBD oil, [previous trials: levetiracetam, lacosamide topiramate, sodium valproate, pyridoxine, gabapentin]	Y (<3)	4	8	6	Severe ID
22	M, 11-15	c.955C>T / p.Q319X	P	N/A	CDH4 (VUS)	Y (Y)	Focal impaired awareness clonic; focal to bilateral tonic-clonic	Sodium valproate, phenobarbital, [levetiracetam, (carbamazepine)]	Y (<3)	4	8	2	Severe ID
23	M, 11-15	c.949+1G>A	LP	N/A	-	Y (Y)	Focal impaired awareness tonic; focal to bilateral tonic-clonic	Carbamazepine, sodium valproate, clobazam	Y (UK)	4	0	1	Severe ID
25	F, 1-5	c.3605del / p.V1202AfS*52	LP	N/A	-	Y (Y)	Focal tonic; focal epileptic spasms	Vigabatrin, sodium valproate, [phenobarbital, vitamin B6, clobazam, ACTH, perimidone, levetiracetam], (phenytoin)	Y (<3)	9	0	1	GDD
26	M, 1-5	c.623G>A / p.C208Y	VUS	N/A	-	Y (N)	Generalized epileptic spasms	Omnacortil, levetiracetam	Y (<3)	1	9	7	GDD
27	M, 1-5	c.949+1G>A	LP	N/A	-	Y (N)	Generalized tonic-clonic	Levetiracetam, sodium valproate	Y (<3)	5	2	0	Severe ID
28	F, 1-5	c.949+1G>A	LP	N/A	-	Y (N)	Focal impaired awareness clonic; focal to bilateral tonic-clonic; generalized tonic-clonic	Levetiracetam, sodium valproate	Y (<3)	5	3	0	GDD
30	M, 1-5	c.3095G>C / p.Arg1032Thr c.3116C>A / p.Thr1039Asn	VUS VUS	N/A N/A	-	Y (Y)	Generalized epileptic spasms	ACTH, sodium valproate, [vigabatrin, topiramate, phensuximide, nitrazepam], (lamotrigine)	N (UK)	5	9	7	GDD