Table 2. Summary of Genes with Variants Identified in our SUDP Cohort and Associated Phenotypes.

We present each case with P/LP variants and VUS-FP implicated in our SUDP cohort by disease categories. ACMG, The American College of Medical Genetics and Genomics. AMP, The Association for Molecular Pathology. AF, allele frequency. P, Pathogenic. LP, Likely pathogenic. VUS, variant uncertain significance. M, male. F, female. URI, upper respiratory infection. GI, gastrointestinal symptoms. VUS-FP are indicated with notes regarding reasons for classifying them as such (column indicated with asterisk): functional evidence,^a validated in an exome-wide approach,^b deleterious splicing variant,^c different missense substitution at the same amino acid position that is established as pathogenic.^d

			Genotypes and ACMG/AMP classification			Phenotypes and clinical history						Neuropathology review
Disease Categories	Gene	Case	Variant	AF in normal population	ACMG/AMP classification and evidence*	Age in months	Sex	Personal and family history	Position discovered	Location discovere d	Shared sleep surface	Bilamination of the dentate gyrus	Abnormal hippocampal architecture
Neurological	ALG13	316	NM_001099922.3:c.2525A>G (p.Gln842Arg)	N	VUS-FPb	9	M	Febrile seizures; velopharyngeal dyscoordination; Maternal and sibling history of childhood seizures	Prone	Crib	N	N	N
	CACNA1A	297	NM_023035.3:c.3377G>A (p.Arg1126His)	0.000036	VUS-FPa	5	F	Paternal history of febrile seizures	Upright	Carseat	N	N/A	N/A
	DEPDC5	156	NM_001242896.3:c.2446C>T (p.Gln816*)	N	LP (PVS1, PM2)	3	F	Antecedent minor illness: URI	Supine	Crib	N	Y	Y
		182	NC_000022.11(NM_001242896.3):c.2105-1G>A	0.000004	LP (PVS1, PM2)	4	M	No pediatric primary care	Supine	Adult bed	Y	N/A	N/A
	DYRK1A	71	NM_001396.4:c.1528A>G (p.Ser510Gly)	N	VUS-FPc	3	M	None	Side	Crib	N	N/A	N/A
	GABRB3	242	NM_000814.6:c.650G>A (p.Arg217His)	0.000044	VUS-FPa	5	M	Concurrent fever at time of death	Side	Adult bed	N	Y	Y
	GABRG2	1	NC_000005.10(NM_198903.2):c.327+1G>A	N	LP (PVS1, PM2)	19	M	Febrile seizures; Family history of childhood epilepsy in mother and maternal grandmother, paternal cousin died of SIDS	N/A, Age	Toddler bed	N	Y	Y
	SCN1A	343	NM_001165963.3:c.182T>C (p.Leu61Pro)	N	LP (PS2, PM2)	20	F	Febrile seizures; concurrent fever at time of death. Male sibling clinically diagnosed with Dravet syndrome	N/A, Age	Adult bed	Y	N	N
		308	NM_001165963.3:c.4357T>G (p.Tyr1453Asp)	N	LP (PS2, PM2)	22	M	None	N/A, Age	Toddler bed	N	N	N
		155	NM_001165963.3:c.2045G>T (p.Gly682Val)	N	LP (PS3, PM2)	2	F	Antecedent minor illness: GI	Supine	Crib	N	N	N
		60	NM_001165963.3:c.3886T>A (p.Leu1296Met)	0.000004	VUS-FPa	2	F	None	Prone	Adult bed	N	N/A	N/A
	SCN4A	70	NM_000334.4:c.2045C>G (p.Ser682Trp)	N	VUS-FPa	3	M	None	Prone	Couch	Y	N	N
	SCN8A	144	NM_001330260.2:c.3284G>A (p.Arg1095Gln)	N	VUS-FPc	1	M	None	Supine	Crib	N	N/A	N/A
Cardiac	AKAP10	295	NM_007202.4:c.850A>G (p.Lys284Glu)	N	VUS-FPb	10	F	None	Supine	Crib	N	Y	Y
	CAV3	329	NM_033337.3:c.260T>C (p.Leu87Pro)	0.000004	VUS-FPa	4	F	None	Prone	Crib	N	N	N
	FLNC	215	NC_000007.14(NM_001458.4):c.3964+5G>A	N	VUS-FPc	6	M	None	Supine	Adult bed	Y	N/A	N/A
	KCNE1	181	NM_000219.6:c.173C>T (p.Thr58Ile)	0.000028	VUS-FPa	2	F	None	Side	Adult bed	Y	N/A	N/A
	MYBPC3	103	NC_000011.10(NM_000256.3):c.821+1G>A	0.000029	P (PS3, PVS1, PP1, PP5)	2	M	None	Supine	Couch	Y	N/A	N
		89	NM_000256.3:c.3791G>A (p.Cys1264Tyr)	N	VUS-FPc	3	F	None	Supine	Couch	Y	N/A	N/A
	PLN	277	NM_002667.5:c.40_42del (p.Arg14del)	N	P (PS3, PM4, PP1, PP5)	6	M	Family history of early cardiac death in 3 maternal family members	Supine	Crib	N	N/A	N/A
	SCN5A	164	NC_000003.12(NM_001099404.1):c.4299+1del	N	LP (PVS1, PM2)	1	F	None	Prone	Couch	Y	Y	Y
		269	NM_001099404.1:c.5287G>A (p.Val1763Met)	N	P (PS3, PS2, PM2)	1	M	Antecedent minor illness: URI	N/A, Awake	N/A	N/A	N/A	N/A
		179	NM_001099404.1:c.4895G>A (p.Arg1632His)	0.000008	VUS-FPa	1	F	Antecedent minor illness: URI	Supine	Couch	Y	N/A	N/A
		152	NC_000003.12(NM_001099404.1 ):c.3840+12C>T	0.000032	VUS-FPc	4	F	None	Supine	Crib	N	N	Y
	TNNI3	2	NM_000363.5:c.433C>T (p.Arg145Trp)	0.000011	P (PS3, PS1, PP1, PP5)	2	F	None	Supine	Playpen	N	N/A	N/A
		330	NM_000363.5:c.556C>T (p.Arg186Trp)	0.000014	VUS-FPd	8	M	Sibling with cardiac concerns lacking definitive diagnosis; Family history of SIDS (maternal cousin)	Supine	Crib	N	N	Y
	TTN	251	NM_001267550.2:c.98299_98300del (p.Arg32767Glyfs*2)	0.000007	P (PVS1, PM1, PP5)	7	M	Paternal history of heart transplant at 29 years old	Supine	Crib	N	Y	Y
		126	NC_000002.12(NM_001267550.2):c.97492+1G>C	N	P (PVS1, PM1, PM2, PP5)	2	M	None	Prone	Caregiver's lap	Y	N	N
		132	NM_001267550.2:c.91721A>T (p.Glu30574Val)	N	VUS-FPc	9	M	Concurrent fever at time of death	Supine	Adult bed	Y	N/A	N/A
		149	NM_001267550.2:c.43622C>T (p.Ser14541Leu)	N	VUS-FPc	5	F	None	Supine	Crib	N	Y	Y
		112	NM_001267550.2:c.64898G>A (p.Arg21633Gln)	N	VUS-FPc	2	M	None	Supine	Adult bed	Y	N/A	N/A
Systemic/Syndromic	ANKRD11	282	NM_001256182.1:c.7534C>T (p.Arg2512Trp)	N	P (PS2, PS1, PM2)	30	M	Tethered cord, vocal cord paralysis, strabismus, ventricular septal defect, aortic root dilation, boney defect at base of skull, hypotonia, developmental delay	N/A, Age	Toddler bed	N	N	Y
	BRPF1	319	NM_001003694.2:c.1182_1183del (p.Ala396Leufs*69)	N	P (PVS1, PS2, PM2)	38	M	Short stature, ptosis, blepharophimosis, broad thumbs, speech delay	N/A, Age	Toddler bed	N	N/A	N/A
	FLNA	339	NM_001110556.2:c.4772C>T (p.Pro1591Leu)	0.000011	VUS-FPb	17	M	Concurrent fever	N/A, Age	Crib	N	Y	N
	KCNJ2	67	NM_000891.3:c.119G>A (p.Arg40Gln)	0.000018	VUS-FPa	5	F	None	Prone	Couch	N	N/A	N/A
	PDHA1	53	NM_001173454.1:c.1246C>T (p.Arg416Cys)	N	P (PS3, PM2, PP1, PP2, PP5)	11	M	Nystagmus; Antecedent febrile illness with fatigue; Histology inconsistent with overwhelming viral illness	Supine	Couch	Y	N/A	N/A
	TCF4	300	NM_001243226.2:c.868T>A (p.Ser290Thr)	N	VUS-FPb	6	M	None	Supine	Adult bed	Y	Y	Y