Table 1.
Disorders detectable by EpiSign v2.
| Disease/disorder | Causative gene(s)/region | New in EpiSign V2 | Validation cohort positives | Clinical cohort positives |
|---|---|---|---|---|
| ɑ-thalassemia/mental retardation X-linked syndrome (ATR-X) | ATRX (301404) | No | 2 | 4 |
| Autism, susceptibility to, 18 (AUT18) | CHD8 (610528) | Yes | 6 | 3 |
| BAFopathies: Coffin–Siris (CSS1–4, and 8) and Nicolaides–Baraitser (NCBRS) syndromes | ARID1B (135900), ARID1A (614607), SMARCB1 (614608), SMARCA4 (614609), SMARCC2 (618362), SMARCA2 (601358) | ARID1A, SMARCC2 | 28 | 10 |
| Blepharophimosis intellectual disability syndrome, SMARCA2 type | SMARCA2 (OMIM not available, PMID: 32694869) | Yes | 2 | |
| Börjeson–Forssman–Lehmann syndrome (BFLS) | PHF6 (301900) | Yes | 1 | |
| Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (ADCADN) | DNMT1 (604121) | No | ||
| CHARGE syndrome | CHD7 (214800) | No | 6 | 4 |
| Cornelia de Lange syndrome (CdLS) | NIPBL (122470), RAD21 (614701), SMC3 (610759), SMC1A (300590) | No | 11 | 6 |
| Down syndrome | Trisomy 21 (190685) | No | 1 | |
| Epileptic encephalopathy, childhood-onset (EEOC) | CHD2 (615369) | Yes | 1 | |
| Floating Harbor syndrome (FLHS) | SRCAP (136140) | No | ||
| Genitopatellar syndrome (GTPTS) and Ohdo syndrome, SBBYSS variant (SBBYSS) | KAT6B (606170; 603736) | No | 3 | 2 |
| Helsmoortel–van der Aa syndrome (HVDAS)a | ADNP (615873) | No | 9 | 2 |
| Hunter–McAlpine syndrome (HMA) | Chr5q35-qter duplication (601379) | Yes | ||
| Immunodeficiency–centromeric instability–facial anomalies syndrome (ICF)b | DNMT3B (242860), CDCA7 (616910), ZBTB24 (614069), HELLS (616911) | Yes | ||
| Kabuki syndrome | KMT2D (147920), KDM6A (300867) | KDM6A | 12 | 5 |
| Kleefstra syndrome | EHMT1 (610253) | Yes | 2 | 2 |
| Koolen–de Vries syndrome (KDVS) | KANSL1 (610443) | Yes | 5 | |
| Mental retardation, autosomal dominant 23 (MRD23) | SETD5 (615761) | Yes | 4 | |
| Mental retardation, autosomal dominant 51 (MRD51) | KMT5B (617788) | Yes | ||
| Mental retardation, X-linked 93 (MRD93) | BRWD3 (300659) | Yes | 1 | 1 |
| Mental retardation, X-linked 97 (MRD97) | ZNF711 (300803) | Yes | 1 | |
| Mental retardation, X-linked syndromic, Nascimento-type (MRXSN) | UBE2A (300860) | Yes | 1 | |
| Mental retardation, X-linked, Snyder–Robinson type (MRXSSR) | SMS (309583) | Yes | 1 | |
| Mental retardation, X-linked, syndromic, Claes–Jensen syndrome (MRXSCJ) | KDM5C (300534) | No | 6 | 1 |
| PCR2 complex (Weaver (WVS) and Cohen–Gibson (COGIS) | EZH2 (277590), EED (617561) | Yes | ||
| Rahman syndrome (RMNS) | HIST1H1E (617537) | Yes | ||
| Rubinstein–Taybi syndrome (RSTS) | CREBBP (180849), EP300 (613684) | Yes | 2 | 3 |
| SETD1B-related syndrome | SETD1B (619000) | Yes | 1 | |
| Sotos syndrome | NSD1 (117500) | No | 8 | 4 |
| Tatton–Brown–Rahman syndrome (TBRS) | DNMT3A (615879) | Yes | 1 | 1 |
| Wiedemann–Steiner syndrome (WDSTS) | KMT2A (605130) | Yes | 3 | 2 |
| Williams–Beuren deletion syndrome (WBS) and Williams–Beuren regions duplication syndrome (Dup7)c | 7q11.23 deletion (194050)/duplication (609757) | No | 2 | |
| Wolf–Hirschhorn syndrome (WHS) | Chr4p16.13 deletion (194190) | Yes | ||
| Fragile X syndrome (FXS) | TNR/FMR1 (300624) | No | 6 | |
| Mental retardation, FRA12A type | TNR/DIP2B (136630) | No | 1 | |
| Angelman syndrome (AS) | ID/UBE3A (105830) | No | 6 | 1 |
| Prader–Willi syndrome | ID/15q11 (SNRPN, NDN) (176270) | No | 3 | |
| Silver–Russell syndrome 1 (SRS1) | ID/11p15.5 (180860) | No | 5 | 1 |
| Beckwith–Wiedemann syndrome (BWS) | ID/11p15 (ICR1, KCNQ1OT1, CDKN1C) (130650) | No | 4 | |
| Silver–Russell syndrome 2 (SRS2) | ID/7p11.2 (180860) | No | ||
| Temple syndrome | ID/14q32 (616222) | No | ||
| Kagami–Ogatta syndrome (KOS) | ID/14q32 (608149) | No | 2 |
OMIM number listed in parentheses adjacent to disorder name. The following list of genes have been classified as having reduced sensitivity and more moderate signatures based on signature strength, limited reference cohort size, or types of variants that have been tested: CHD8, PHF6, DNMT3B, CDCA7, ZBTB24, HELLS, SETD5, KMT5B, BRWD3, ZNF711, KAT6B, SMS, DNMT3A.
ID imprinting disorder, TNR trinucleotide repeat disorder.
aADNP has two distinct signatures depending on where in the gene the variant occurs. HVDAS_T signature includes variants that occupy the N- and C-terminus of the gene and HVDAS_C includes variants in the central region of the gene including the nuclear localization signal of the protein.
bICF1 exhibits one signature while ICF 2, 3, and 4 exhibit a separate, common signature.
cThese two deletion/duplication syndromes exhibit symmetrical increased/decreased DNA methylation signatures, respectively.