. 2020 Feb 27;106(3):356–370. doi: 10.1016/j.ajhg.2020.01.019

Table 1.

Description of the Study Cohort

Syndrome/Episignature	Abbreviation	Underlying Genes	Phenotype MIM Number	Training Cohort	Testing Cohort	Episignature Detected?
ADNP syndrome—5′ and 3′ terminal ends	ADNP_T	ADNP (outside c.2000-2340)	615873	14	5	yes
ADNP syndrome—central	ADNP_C	ADNP (c.2000-2340)	615873	10	3	yes
alpha-thalassemia mental retardation syndrome	ATRX	ATRX	301040	13	5	yes
autism, susceptibility to, 18	AUTS18^a	CHD8	615032	5	0	yes
BAFopathies: Coffin-Siris 1–4 (CSS1–4) and Nicolaides-Baraitser (NCBRS) syndromes	BAFopathy^a	ARID1A^a, ARID1B, SMARCB1, SMARCA4, SMARCA2	614607, 135900, 614609, 614608, 601358	50	19	yes
Börjeson-Forssman-Lehmann syndrome	BFLS^a	PHF6	301900	4	0	yes
cerebellar ataxia, deafness, and narcolepsy, autosomal dominant	ADCADN	DNMT1	604121	5	0	yes
CHARGE syndrome	CHARGE	CHD7	214800	45	15	yes
Chr7q11.23 duplication syndrome	Dup7	Chr7q11.23 duplication	609757	8	2	yes
mental retardation, X-linked, syndromic, Claes-Jensen type (Claes-Jensen syndrome)	CJS	KDM5C	300534	26	8	yes
Cornelia de Lange syndrome 1–4	CdLS	NIPBL, RAD21, SMC3, SMC1A	122470, 614701, 610759, 300590	31	10	yes
Down syndrome	Down	Chr21 trisomy	190685	29	10	yes
epileptic encephalopathy, childhood-onset	EEOC^a	CHD2	615369	5	0	yes
Floating-Harbor syndrome	FHS	SRCAP	136140	15	5	yes
genitopatellar syndrome	GTPTS	KAT6B	606170	5	0	yes
Hunter McAlpine syndrome	HMA^a	17q23.1-q24.2 duplication involving NSD1	601379	4	0	yes
immunodeficiency-centromeric instability-facial anomalies syndrome 1	ICF1	DNMT3B	242860	8	0	yes
immunodeficiency-centromeric instability-facial anomalies syndrome 2–4	ICF2_3_4	CDCA7, ZBTB24, HELLS	614069, 616910, 616911	7	0	yes
Kabuki syndrome 1 and 2	Kabuki^a	KMT2D, KDM6A^a	147920, 300867	66	21	yes
Kleefstra syndrome 1	Kleefstra1^a	EHMT1	610253	15	5	yes
Koolen de Vreis syndrome	KDVS^a	KANSL1	610443	6	0	yes
mental retardation, autosomal dominant 51	MRD51^a	KMT5B	617788	5	0	yes
mental retardation, X-linked 93	MRX93^a	BRWD3	300659	5	0	yes
mental retardation, X-linked 97	MRX97^a	ZNF711	300803	13	4	yes
mental retardation, X-linked syndromic, Nascimento-type	MRXSN^a	UBE2A	300860	3	0	yes
mental retardation, X-linked, Snyder-Robinson type	MRXSSR^a	SMS	309583	8	2	yes
Rahman syndrome	RMNS^a	HIST1H1E	617537	6	0	yes
Rubinstein-Taybi syndrome 1 and 2	RSTS^a	CREBBP, EP300	180849, 613684	30	9	yes
SBBYSS syndrome	SBBYSS^a	KAT6B	603736	7	0	yes
SETD1B-related syndrome	SETD1B^a	SETD1B	N/A	8	0	yes
Sotos syndrome	Sotos	NSD1	117550	47	15	yes
Tatton-Brown-Rahman syndrome	TBRS^a	DNMT3A	615879	10	4	yes
Wiedemann-Steiner syndrome	WDSTS^a	KMT2A	605130	12	4	yes
Williams syndrome	Williams	Chr7q11.23 deletion	194050	15	6	yes
Cornelia de Lange syndrome 5 (females only)	CdLS5	HDAC8	300882	8	N/A	no
FG syndrome 1	FG1^a^,^b	MED12	305450	9	N/A	no
Glass syndrome	Glass^a^,^b	SATB2	612313	9	N/A	no
KMT2C-related syndrome^£	KMT2C^a^,^b^,^c	KMT2C	617768	4	N/A	no
neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	NEDCFSA^a^,^b	KDM6B	618505	5	N/A	no
Rett syndrome	Rett	MECP2	312750	36	N/A	no
Siderius-type X-linked syndromic mental retardation	MRXSSD^a^,^b	PHF8	300263	9	N/A	no
Smith-Magenis syndrome	SMS^a^,^b	RAI1	309583	15	N/A	no

Indicates that these disorders (or some of their subtypes) were not evaluated in previous studies.

Indicates cohorts with no evidence of a reproducible episignature; this is potentially due to small sample size. A possibility of an episignature is not completely ruled out, and reanalysis using larger sample sizes is warranted.

The OMIM database, at the time of this study, has indicated that subjects with KMT2C mutations may be said to have “Kleefstra 2” syndrome. The DNA methylation signature found in Kleefstra 1 (caused by EHMT1), however, is completely absent in these subjects. It is acknowledged that these subjects have a distinct phenotype from Kleefstra syndrome and a name change is currently in process with OMIM. The numbers in the testing and training cohort columns indicate the sample counts available for each condition in each category. For cohorts with negative findings in the initial assessment, we did not further split the data into testing and training, and thus, the values in the testing column are indicated with N/A (not applicable).