SETBP1 Mutations
| SETBP1 Variant p.xxx | SETBP1 Location/Coding DNA c.xxx | Condition | Inherited Form | Clinical Significance | Source | Comments | No of Cases | Order |
|---|---|---|---|---|---|---|---|---|
| p.Gly15Argfs*47 | c.39_40del | SETBP1-HD | de novo/not inherited | pathogenic | COE/DNA08-08272/Morgan 2021 | The mutation is predicted to cause a frameshift in the SETBP1 protein leading to a stop codon after 42 residues.In a 9-year-old male with mild intellectual disability, ADHD, behavioral difficulties, speech and motor delays, dysmorphic facial features, and seizures or abnormal EEG. | 1 | 15 |
| p.Arg143Valfs | c.427delC | SETBP1-HD | de novo/not inherited | pathogenic | COE/Troina 3097/Clinvar: 2117731 | In a 34-year-old female with severe intellectual disability, speech and motor delays, dysmorphic facial features, and seizures or abnormal EEG. | 1 | 143 |
| p.Trp274Ter | c.821G>A | SETBP1-HD | de novo/not inherited | pathogenic | COM4, Jansen 2021:pt19, COM226 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 2 | 274 |
| p.Leu411Glyfs*6 | c.xxx | SETBP1-HD | de novo/not inherited | pathogenic | COE/DNA-008897 | The mutation is predicted to cause a frameshift in the SETBP1 protein leading to a stop codon after 6 residues.In a 73-year-old male with profound intellectual disability, social difficulties, behavioral difficulties, speech and motor delays, and dysmoprphic facial features. | 1 | 411 |
| p.Gln422Ter | c.1264C>T | SETBP1-HD | don't know | pathogenic | CLINVAR: SCV000681377.1 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 422 |
| p.His523Leufs*32 | c.1568delA | SETBP1-HD | de novo/not inherited | pathogenic | COM5, Jansen 2021:pt16, COM168 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay | 2 | 523 |
| p.Trp532Ter | c.1596G>A | SETBP1-HD | de novo/not inherited | pathogenic | COE/Troina 1274 | In a 19-year-old male with severe intellectual disability, behavioral difficulties, speech and motor delays, and dysmorphic facial features. | 1 | 532 |
| p.Pro559Argfs | c.1676delC | SETBP1-HD | don't know | pathogenic | CLINVAR: SCV000572657.4, COM27, Jansen 2021:pt18 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 559 |
| p.Gly588AspFs*42 | SETBP1-HD | de novo/not inherited | pathogenic | COM/Searchlight | The mutation is predicted to cause a frameshift in the SETBP1 protein leading to a stop codon after 42 residues. | 1 | 588 | |
| p.R589* | c.1765C>T | SETBP1-HD | de novo/not inherited | pathogenic | Decipher: 276824, COM7, Leonardi 2020 p1, COM114, COM165, COM176, COM186, COM232 | Broad hallux, Broad thumb, Bulbous nose, Cleft palate, Hypertelorism, Moderate global developmental delay, Prominent nasal bridge (other child: mild intellectual disability, he still presented language impairment and manifested motor hindrance. He never presented seizures; the EEG was normal while the brain MRI highlighted a thin corpus callosum and a rotated hippocampal tail. At physical examination, dysmetrya of the lower limbs (1 cm), short lingual frenulum, and phimosis, were observed. Subtle facial dysmorphisms were present, which included long face, high forehead, thin upper lip, smooth philtrum, and mild micrognathia. Five café-au-lait spots, fetal pads, and dorsal hirsutism were noted. No other problems were reported, other than color blindness and farsightedness.) | 7 | 589 |
| p.Lys592Ter | c.1774A>T | SETBP1-HD | de novo/not inherited | pathogenic | Rauch BO22/10 | intellectual disability & autism | 1 | 592 |
| p.Ser608AlafsTer22 | c.1821delC | SETBP1-HD | de novo/not inherited | pathogenic | Hamdan 2014, COM8 | The mutation is predicted to cause a frameshift in the SETBP1 protein leading to a stop codon after 22 residues.In a 6-year-old male with intellectual disability, speech motor delays, and delayed myelination. | 1 | 608 |
| p.Arg625Ter | c.1873C>T | SETBP1-HD | de novo/not inherited | pathogenic | COE/DNA11-21308Z, COM1, COM2, COM3, GROVEZA, COM88, COM249 (inherited), COM250, Wan 2023 (2) | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R625X pathogenic variant in the SETBP1 gene has been reported in five unrelated individuals with intellectual disability (Coe et al., 2014; Grozeva et al., 2015., and SETBP1 community. | 10 | 625 |
| p.Arg626Ter | c.1876C>T | SETBP1-HD | de novo/not inherited | pathogenic | COE/DNA11-19324Z, CLINVAR:SCV000329813.5, SCV000329813.6, SCV000893495.1, COM20, COM85, COM152, COM191, COM195, COM207, COM275 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. One individual also has pathogenic variants in SLC19A3 and STXBP2 genes. | 9 | 626 |
| p.Lys673Ter | c.2016_2017insT | SETBP1-HD | de novo/not inherited | pathogenic | CLINVAR: SCV000494650.1 | Patient with intellectual disability. MRD29 is caused by heterozygous mutation in SETBP1 gene. This mutation is predicted to cause a truncated and non-functional SETBP1 protein. | 1 | 673 |
| p.S772L | c.2315C>T | SETBP1-related disorderss | inherited | uncertain significance | COM9 (note parent and 2 children have this same variant) | This mutation is listed as uncertain signficance as the individual has 2 mutations and parent does not show signs of SETBP1 disorder. | 1 | 772 |
| p.Ile822fs | c.2464delA | SETBP1-HD | de novo/not inherited | pathogenic | COE/DNA03-00335, COM10 | In a 14-year-old boy with a normal IQ but with speech delay, motor delay, behavioral difficulties, and dysmorphic facial features. The patient's IQ was 76, which is in the borderline range, but was 'disharmonic.' The patient had speech impairment, with first words at 18 months but almost no speak until age 4 years. At age 14 he spoke but was hard to understand, with words in the wrong order and difficulty finding words. He was diagnosed with ADHD, for which he was treated with methylphenidate. Growth parameters were within normal limits. Brain MRI was normal. | 1 | 822 |
| p.Glu858Lys | c.2572G>A | SETBP1-related disorders | de novo/not inherited | pathogenic | CLINVAR: SCV000741799.1, Decipher: 279312, COM18, COM55, COM120, COM125, COM148, COM163, De Rubeis 2014, Leondardi 2020, COM229, COM246, COM259 | Inborn genetic diseases (yes) Neurologic (child onset) (yes) MR/ID/DD (yes) prominent forehead hypotonia (yes) | 12 | 858 |
| p.Asp874Gly | c.2621A>G | SETBP1-related disorders | de novo/not inherited | pathogenic | COM10 | 1 | 874 | |
| p.Ser1011Ter | SETBP1-HD | de novo/not inherited | pathogenic | COE/Troina 1512 | In a 17-year-old male with mild intellectual disability, ADHD, social difficulties, speech and motor delays, and dysmorphic facial features. | 1 | 1011 | |
| p.Met470Ter | c.1408delA | SETBP1-HD | don't know | pathogenic | CLINVAR: SCV000741135.1, COM16 | MR/ID/DD (yes) Dysmorphic features (yes) FTT/Undergrowth (yes) Hypotonia (yes) Neurologic (child onset) (yes) | 1 | 470 |
| p.Glu545Ter | c.1633G>T | SETBP1-HD | de novo/not inherited | pathogenic | CLINVAR: SCV000748273.1, COM43, Jansen 2021:pt14 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 545 |
| p.Arg1588X | unknown | SETBP1-HD | inherited | pathogenic | O'Roak 2012 14012.p1 | nonsense mutation in male with autism w/unaffected sibling. Abnormality of the palpebral fissures, delayed fine motor development, severe expressive language delay, short attention span. inherited from mother | 1 | 1588 |
| SETBP1 167.44 kb deletion | 18:42108088-42275522 | SETBP1-HD | don't know | pathogenic | DDD GRCh37 | Female with Abnormal eyebrow morphology; Brachydactyly; Conspicuously happy disposition; Drooling; Global developmental delay; Hypertelorism; Hypoplastic nasal bridge; Low frustration tolerance; Recurrent otitis media; Smooth philtrum | 1 | 9999 |
| p.IIe871Ser | c.2612 T>G | Schinzel-Giedion syndrome (classic) | de novo/not inherited | likely pathogenic | Personal or Family Member's Genetic Report | This mutation is likely pathogenic and causative for Schinzel-Giedion syndrome but the affected child might have a mild phenotype. | 1 | 871 |
| p.Ser869Asn | c.2606G>A | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC1 | In a 4-year-old female with developmental delay, seizures, cardiac defects, scoliosis, hydronephrosis, microcephaly, and characteristic Schinzel-Giedion facial features. | 1 | 869 |
| p.Asp868Asn | c.2602G>A | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC2 | In a 10-month-old female with developmental delay, seizures, cardiac defects, hydronephrosis, hearing impairment, microcephaly, and characteristic Schinzel-Giedion facial features. | 1 | 868 |
| p.Ile871Thr | c.2612T>C | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC3 | In a 24-month-old male with developmental delay, seizures, cardiac defects, vision impairment, hearing impairment, hydronephrosis, microcephaly, and characteristic Schinzel-Giedion facial features. | 1 | 871 |
| p.Gly870Asp | c.2609G>A | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC4, Herenger C1, Acuna-Hidalgo CC9 | In a 5-year-old male with developmental delay, seizures, spina bifida occulta, hydronephrosis, hearing impairment, microcephaly, and characteristic Schinzel-Giedion facial features. In a 15-year-old male with developmental delay, seizures, underdeveloped corpus callosum, hydronephrosis, ventriculomegaly, vision impairment, hearing impairment, and characteristic Schinzel-Giedion facial features. In a 6-year-old male with developmental delay, seizures, underdeveloped corpus callosum, hydronephrosis, scoliosis, vision impairment, and characteristic Schinzel-Giedion facial features. | 1 | 870 |
| p.Ile871Thr | c.2612T>C | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC5 | In a female with developmental delay, seizures, hydronephrosis, hearing impairment, underdeveloped corpus callosum, microcephaly, and characteristic Schinzel-Giedion facial features. | 1 | 871 |
| p.Ser869Arg | c.2607C>G | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC10 | In a 5-month-old female with developmental delay, seizures, hydronephrosis, ventriculomegaly, and characteristic Schinzel-Giedion facial features. | 1 | 869 |
| p.Asp868Ala | c.2603A>C | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Hoischen C7 | In a 10-month-old female with developmental delay, seizures, cardiac defects, hydronephrosis, microcephaly, and characteristic Schinzel-Giedion facial features. | 1 | 868 |
| p.Ser867Arg | c.2601C>A | Schinzel-Giedion syndrome (atypical) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC27, Carvalho C1 | In a 4-year-old female with seizures, cardiac defects, scoliosis, microcephaly, and characteristic Schinzel-Giedion facial features. In a 3-year-old female with developmental delay, seizures, vision impairment, mid-face retraction, upslanting palpebral fissures, and micro/retrognathia. | 2 | 867 |
| p.Glu862Lys | c.2584G>A | Schinzel-Giedion syndrome (atypical) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC28 | In a 6-year-old female with developmental delay, vision impairment, microcephaly, prominent forehead, mid-face retraction, and macrostomia. | 1 | 862 |
| p.Thr873Ile | c.2618C>T | Schinzel-Giedion syndrome (atypical) | de novo/not inherited | pathogenic | Acuna-Hidalgo CC29 | In a 3-year-old male with developmental delay, cortical atrophy, and some characteristic Schinzel-Giedion facial features. | 1 | 873 |
| p.P594Lfs*36 | c.1781del | SETBP1-HD | de novo/not inherited | pathogenic | Eising 2018 p2 | developmental delay and childhood apraxia of speech; late onset language use; listening comprehension scales standard scores <85; IQ lower extreme; oral expression scales standard scores <85; gross or fine motor impairment; oral nonverbal motor impairment; dysarthria | 1 | 594 |
| p.Asp900ThrfsTer61 | c.2697del | SETBP1-HD | de novo/not inherited | pathogenic | Decipher: 370904/ | Phenotype: Compulsive behaviors ; Global developmental delay ; Hallux valgus ; High, narrow palate ; Severe expressive language delay | 1 | 900 |
| SETBP1 240.46 kb deletion | hg19 18q12.3(42314546-42555001) | SETBP1-HD | de novo/not inherited | likely pathogenic | Decipher: 331454 | Delayed speech and language development | 1 | 9999 |
| p.Gly719GlufsTer65 | c.2156del | SETBP1-HD | de novo/not inherited | likely pathogenic | Decipher: 281144, COM44, Jansen 2021:pt9 | apraxia, attention deficit hyperactivity disorder, cognitive impairment, joint hypermobility | 1 | 719 |
| p.Ser854Cys | C.2561C>G | SETBP1-related disorders | de novo/not inherited | pathogenic | Decipher: 258819, COM205 | Delayed speech and language development, Intellectual disability, Joint hypermobility, Nephrocalcinosis, Velopharyngeal insufficiency, Widely spaced teeth | 2 | 854 |
| p.S854F | c.2561C>T | SETBP1-related disorders | de novo/not inherited | pathogenic | Personal or Family Member's Genetic Report, COM17, COM175 | Failure to thrive, feeding problems, hypotonia from birth, epilepsy with continuous spike wave during slow-wave sleep and ESES EEG's, absence seizures, hemangiomas, regression, global developmental delay, ataxic gait, speech delay, recurrent fevers, GI issues. Pat2: milder impact no seizures, and has a VUS variant in CHD8 and CALC genes | 2 | 854 |
| 986.27 kb deletion including SETBP1 | hg19 18q12.3(42028936-43015201) | SETBP1-HD | de novo/not inherited | pathogenic | Decipher:253969, Filges p1 | Delayed speech and language development, intellectual disability, distinctive facial features with an inverted triangle face, prominent forehead, ptosis with periorbital fullness, epicanthus and pointed chin | 2 | 9999 |
| 850 kb deletion including SETBP1 | hg18 18q12.3(40233803-41088224) | SETBP1-HD | de novo/not inherited | pathogenic | Filges p2 | expressive language delay, delayed motor development, difficulty concentrating, mild facial differences | 1 | 9999 |
| p.Gln89Ter | c.265 C>T | SETBP1-HD | de novo/not inherited | pathogenic | Simons VIP Registry 02-19-01/COM12/clinvar: RCV000760733.1/clinvar: RCV001265338.1 | Low muscle tone, speech delay, delayed myelination | 1 | 89 |
| p.Asp900Gly | c.2699A>G | SETBP1-related disorders | de novo/not inherited | uncertain significance | Simons VIP Registry 02-19-02, COM11 | 1 | 900 | |
| p.Leu957Pro | 2870C>T/2870T>G | SETBP1-related disorders | de novo/not inherited | pathogenic | Simons VIP Registry 02-19-03, COM14, Wong, COM220 | 2 | 957 | |
| p.xxx | c.4000+2T>G intronic alteration | SETBP1-related disorders | de novo/not inherited | likely pathogenic | Clinvar: 984999/COM19 | The alteration is predicted to abolish the native donor splice site. Alterations that disrupt the canonical splice donor site are typically deleterious in nature. Associated with moderate intellectual disability, scoliosis, cerebral palsy, hearing loss, vision problems, small in stature, pervasive developmental disorder, Sex: male, Ambry Genetics | 1 | 2000 |
| p.q593* | c.1777c>t | SETBP1-HD | de novo/not inherited | pathogenic | Client's Genetic Report, COM15, Jansen 2021:pt20 | 1 | 593 | |
| p.Arg530ter | c.1588C>T | SETBP1-HD | de novo/not inherited | likely pathogenic | Personal or Family Member's Genetic Report, Decipher: 305600, COM13, COM67, COM97, COM141, COM139, Patient report-COM149, COM256, COM300 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Abnormality of the palpebral fissures, Delayed fine motor development, Severe expressive language delay, Short attention span / Phenotype: hypotonia, delayed motor skills, sleep problems, vision problems and behavior challenges | 8 | 530 |
| p.Thr1387Me | c.4160C>T | SETBP1-related disorders | de novo/not inherited | uncertain significance | CLINVAR: SCV000747634.1 | Seizures (yes) Delayed speech and language development (yes) Macrocephalus (yes) Joint laxity (yes) Generalized joint laxity (yes) | 1 | 1387 |
| p.Trp222Ter | c.666G>A | SETBP1-HD | de novo/not inherited | pathogenic | CLINVAR: SCV000890566.1, COM41 | This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 222 |
| p.Arg544Ter | c.1630C>T | SETBP1-HD | de novo/not inherited | pathogenic | Client's Genetic Report, COM15, Jansen 2021:pt20, Liu et al (2025) | The R544X nonsense variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Abnormal fear-induced behavior ; Downslanted palpebral fissures ; Dysarthria ; Intellectual disability, moderate ; Tall chin | 4 | 544 |
| p.Arg1583GlyfsTer2 | c.4744del | SETBP1-HD | don't know | likely pathogenic | Decipher: 267428, Other pathogenic deletion: 19:12634389-13265544 GRCh38 | Deep palmar crease, Intellectual disability, moderate, Large for gestational age, Macrocephaly at birth, Overgrowth, Prominent forehead, Sparse scalp hair, Spasticity | 1 | 1583 |
| p.Tyr892Ter | c.2676C>G | SETBP1-HD | don't know | likely pathogenic | Decipher: 304078 | Abnormality of the pinna, Cognitive impairment, Delayed speech and language development, Hypertelorism, Mild global developmental delay, Prominent nasal bridge, Renal cyst, likely LOF | 1 | 892 |
| p.V610RfsX12 | c.1827dupC | SETBP1-HD | don't know | pathogenic | Personal or Family Member's Genetic Report, COM21 | Individual is heterozygous for a pathogenic variant in SETBP1 gene. c.18727dupC pathogenic variant has not been previously reported but is consistent with SETBP1 related disorder | 1 | 610 |
| 372 kb deletion of SETBP1 & SLC14A2 & MicroRNA (MIR5319) | hg18 18q12.3(40,786,241-41,158,305) | SETBP1-HD | de novo/not inherited | pathogenic | Marseglia 2012 | a 15 year old male with adhd, autism, behavior challenges, speech delay, seizures, and social challenges | 1 | 9999 |
| p.R889X | c.C2665T | SETBP1-HD | de novo/not inherited | pathogenic | Eising & Fisher 2015, COM225, COM281, COM291 | a female identified with childhood apraxia of speech, together with oral apraxia, dysarthria, moderate ID, seizures and motor impairments, de novo LoF mutation, ovel premature stop variant | 4 | 889 |
| p.Arg1146Trp | C.3436C>T | SETBP1-related disorders | inherited | uncertain significance | Personal or Family Member's Genetic Report, COM 22 | EpiSeek 12.17.13 | 1 | 1146 |
| p.H1167N | C.3499C>A | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM23 | female, autism, GeneDX | 1 | 1167 |
| p.Gln1210Glu | c.3628C>G | SETBP1-related disorders | inherited | uncertain significance | COM25 | 1 | 1210 | |
| p.(Lys1437Glu) | c.4309A>G | SETBP1-related disorders | de novo/not inherited | pathogenic | Strauss 2018 pt23, COM | 1 | 1437 | |
| p.His930Thrfs*31 | c.xxx | SETBP1-HD | de novo/not inherited | pathogenic | COM68 (Personal or Family Member's Genetic Report) | 1 | 930 | |
| p.Leu554fs | c.1661delT | SETBP1-HD | don't know | pathogenic | Clinvar: 524046 | This variant causes a frameshift starting with codon Leucine 554, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Leu554ArgfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 554 |
| p.Lys673fs*33 | c.2017_2018delAA | SETBP1-HD | don't know | likely pathogenic | COM 70/CLINVAR: SCV001168395.1 | The c.2017_2018delAA variant causes a frameshift starting with codon Lysine 673, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 33 of the new reading frame, denoted p.Lys673GlufsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 1 | 673 |
| p.Asp757CysfsX23 | c.2269_2281del | SETBP1-HD | de novo/not inherited | pathogenic | CLINVAR: RCV001008193.1, COM71, COM202 | The c.2269_2281del13 variant causes a frameshift starting with codon Aspartic acid 757, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 23 of the new reading frame, denoted p.Asp757CysfsX23. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. | 2 | 757 |
| Partial Deletion of SETBP1 | hg19 18q12.3(42225174-42304325) | SETBP1-HD | don't know | pathogenic | CLINVAR | submitted by Quest Diagnostics Nichols Institute San Juan Capistrano | 1 | 9999 |
| p.Gln178* | c.532C>T | SETBP1-HD | de novo/not inherited | pathogenic | Simons Searchlight/COM65 | 1 | 178 | |
| p.xxx | c.487-1G>A | SETBP1-related disorders | inherited | uncertain significance | CLINVAR: SCV001815700.1, SCV000582113.4 | The inherited heterozygous c.487-1G>A splice site variant identified in the SETBP1 gene is located in intron 2 of 5 (at intron 2/exon 3 splice site). It destroys the canonical splice acceptor site and is predicted to cause abnormal splicing of SETBP1mRNA. This variant has been reported in ClinVar database as likely pathogenic (ClinVar ID: 429524). The variant has also been reported in a patient with ovarian serous cystadenocarcinoma with no mention of aneurological abnormality [PMID: 29625052]. The c.487-1G>A variant has 0.00005913 allele frequency in the gnomAD(v3) database (9 out of 152,212 heterozygous alleles). Given that the variant is inherited from asymptomatic parent, its presence in multiple individuals in gnomAD database which presumably doesn’t include patients affected with early onset disorders, lack of sufficient evidence of reduced penetrance, and in the absence of any functional studies, we interpret the c.487-1G>A splice site variant as a variant of uncertain significance in the context of an early onset neurological disorder. / Canonical splice site variant predicted to result in an in-frame deletion exon 3; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29625052) | 1 | 2000 |
| p.Asp868His | c.2602G>C | Schinzel-Giedion syndrome (classic) | de novo/not inherited | likely pathogenic | CLINVAR: SCV000194892.1 | 1 | 868 | |
| p.Gly872Arg | c.2614G>A | Schinzel-Giedion syndrome (atypical) | de novo/not inherited | likely pathogenic | CLINVAR: SCV000747633.1 | Abnormality of the nail Cerebral atrophy Atrial septal defect Hydronephrosis Hypospadias, penile Large fontanelles Midface retrusion Teratoma | 1 | 872 |
| p.Tyr1066Ter | c.3198C>A | SETBP1-HD | don't know | pathogenic | CLINVAR: SCV001369498.1 | Intellectual disability Febrile seizures | 1 | 1066 |
| p.(Arg143Cys) | c.427C>T | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM26 | 1 | 143 | |
| p.Arg623fs | c.1867_1871del | SETBP1-HD | don't know | pathogenic | COM73 | 1 | 623 | |
| p. (Pro252Leufs * 91) | c.755_756delinsT | SETBP1-HD | de novo/not inherited | pathogenic | COM74, Jansen 2021:pt12 | 1 | 252 | |
| p.R243LfsX98 | c.726_732del | SETBP1-HD | de novo/not inherited | pathogenic | COM61, Jansen 2021:pt22 | 1 | 243 | |
| p.(Leu577GlnfsTer20) | c.1730_1749del | SETBP1-HD | don't know | pathogenic | LOVD3: 299426, Morgan 2021:pt20 - COM238 | 1 | 577 | |
| p.Gly1268Leufs*26 | c.3770_3800dup | SETBP1-HD | de novo/not inherited | likely pathogenic | LOVD3: 368374, CLINVAR: SCV001446475.1. COM79 | Individual: 00163908, Global developmental delay (HP:0001263); Muscular hypotonia (HP:0001252) / Muscular hypotonia (yes) Global developmental delay (yes) Delayed speech and language development (yes) Abnormality of the face (yes) EEG abnormality (yes) | 1 | 1268 |
| p.(Tyr994Ter) | c.2982C>G | SETBP1-HD | de novo/not inherited | pathogenic | COM74, Jansen 2021:pt24 | 1 | 994 | |
| p.(Arg891Glyfs*70) | c.2671del | SETBP1-HD | don't know | pathogenic | LOVD3: 144433/Clnvar: RCV001268435.2 | Individual 144433, Intellectual disability (HP:0001249); Global developmental delay (HP:0001263) | 1 | 891 |
| p.(Arg67Trp) | c.199C>T | SETBP1-related disorders | don't know | uncertain significance | COM84 | 1 | 67 | |
| p.Glu734Alafs*18 | c.2199_2203del | SETBP1-HD | de novo/not inherited | pathogenic | Aspromonte (2019) 2274.01 | moderate intellectual disability, medium-severe attention deficit, expressive language disorder, dyspraxia. The boy also suffers from generalized anxiety disorder and shows oppositional-provocative behavioral traits. | 1 | 734 |
| p.His210Thrfs | c.628delC | SETBP1-HD | inherited | pathogenic | Silvia Souza da Costa & Profa. Dra. Carla Rosenberg study (2018) | 2 siblings have this and it was inherited through maternal germline mosaicism | 2 | 210 |
| p.G64D | c.191 G>A | SETBP1-related disorders | de novo/not inherited | uncertain significance | Personal or Family Member's Genetic Report | Speech/Language delay. Autism like behavior. | 1 | 64 |
| p.His1116Arg | c.3347A>G | SETBP1-related disorders | inherited | uncertain significance | Leonardi 2020 pt7 | maternally inherited | 1 | 1116 |
| p.Glu16fs | c.44dup | SETBP1-HD | don't know | pathogenic | Clinvar: SCV001374145.1 (Invitae)/ Clinvar: SCV002578134 | This sequence change creates a premature translational stop signal (p.Glu16Argfs*47) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SETBP1-related conditions. Loss-of-function variants in SETBP1 are known to be pathogenic (PMID: 21037274, 25217958). For these reasons, this variant has been classified as Pathogenic. Symptoms from Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin: Global developmental delay (present) , Craniosynostosis syndrome (present) , Enlarged tonsils (present) | 2 | 16 |
| p.Gln186Ter | c.556C>T | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: SCV001434547.1, Zou 2021 | intellectual disability present, submitted by Diagnostic Laboratory, Strasbourg University Hospital, epilepsy/partial seizure Zou | 1 | 186 |
| p.Phe362fs | c.1082_1083dup | SETBP1-HD | don't know | pathogenic | Clinvar: SCV001428814.1 | 1 | 362 | |
| p.Ser397Ter | c.1190C>A | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: SCV001428377.1 | 1 | 397 | |
| p.Glu472fs | c.1414_1417del | SETBP1-HD | de novo/not inherited | likely pathogenic | Clinvar: SCV001450708.1 | 1 | 472 | |
| p.Gln809Ter | c.2425C>T | SETBP1-HD | don't know | pathogenic | Clinvar: SCV001150252.1, COM251 | 2 | 809 | |
| p.Tyr1051fs | c.3151dup | SETBP1-HD | don't know | likely pathogenic | Clinvar: SCV001447024.1 | Strabismus (yes) Behavioral abnormality (yes) Delayed speech and language development (yes) Intellectual disability (yes) | 1 | 1051 |
| p.Pro839fs | c.2516del | SETBP1-HD | don't know | likely pathogenic | Clinvar: RCV001257736.2 | Macrocephaly (yes) moderate intellectual disability (yes) attention deficit (yes) normal MRI (yes) delayed walking (18 months old) (yes) poor language (yes) Age: 50-59 years Sex: male | 1 | 839 |
| p.Gly1052fs | c.3155_3159del | SETBP1-HD | don't know | likely pathogenic | Clinvar: RCV001375032.1 | 1 | 1052 | |
| p.Ser854Tyr | c.2561C>A | SETBP1-related disorders | de novo/not inherited | likely pathogenic | Clinvar: SCV001451597.1 | The SETBP1 c.2561C>A (p.Ser854Tyr) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. The variant is located in exon 4, in the SKI homologous region, a domain that has been identified as a mutational hotspot associated with Schinzel-Giedion syndrome (Carvalho et al. 2015). Based on the identification of the variant in a de novo state, its location in a mutational hotspot, and its absence from the population databases, the p.Ser854Tyr variant is classified as likely pathogenic for Schinzel-Giedion syndrome. | 1 | 854 |
| p.Ter1597TrpextTer7 | c.4790_*9del | SETBP1-HD | de novo/not inherited | likely pathogenic | SS registry/Clinvar: RCV001265510.1/COM252 | 1 | 1597 | |
| p.I871S | c.xxx | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Sullivan 2020, COM101 | First report of a forme-fruste phenotype in a patient with a pathogenic variant within the SGS hotspot on the SETBP1 gene. An echocardiogram and electrocardiogram were normal. Nephrology evaluation noted normal renal function, blood pressure, and renal ultrasound. She is now 7 years old and attending school in a special education classroom. She runs, climbs, and engages simple conversation. She displays a level of functioning that is reflective of moderate intellectual disability, with no regression. | 2 | 871 |
| p.I871S | c.xxxx | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Takeuchi 2015 | 2 | 871 | |
| p.Asp868Glu | c.2604C>A | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | COM103 | atypical presentation | 1 | 868 |
| p.Asp868Tyr | c.2602G>T | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | COM104 | 1 | 868 | |
| p.Lys435Glu | c.1303A>G | SETBP1-related disorders | don't know | uncertain significance | COM105 | 1 | 435 | |
| p.T873A | c.xxx | Schinzel-Giedion syndrome (atypical) | de novo/not inherited | pathogenic | COM99 | 1 | 873 | |
| p.Q1575RfsX5 | c.4723delC | SETBP1-related disorders | don't know | uncertain significance | COM98 | 1 | 1575 | |
| p.D874fs | c.2622delC | SETBP1-HD | don't know | likely pathogenic | not published COM96? | 1 | 874 | |
| p.Lys624Arg | c.1871A>G | SETBP1-related disorders | don't know | uncertain significance | COM95 | 1 | 624 | |
| p.Glu734Alasfs19* | c.2199_2203del | SETBP1-HD | de novo/not inherited | pathogenic | Leondardi pt2 | 1 | 734 | |
| p.F894X | c.2681_2682deITT | SETBP1-HD | de novo/not inherited | pathogenic | COM93, COM154 | 2 | 894 | |
| p.Pro906Leu | c.2717C>T | SETBP1-related disorders | inherited | uncertain significance | COM91 | 1 | 906 | |
| p.Lys469Gln | c.1405A>C | SETBP1-related disorders | inherited | uncertain significance | COM90 | 1 | 469 | |
| p.Leu682Ilefs*9 | c.2044_2046delinsAT | SETBP1-HD | don't know | pathogenic | Jansen 2021:pt3 & pt4 | inheritance unknown (parents deceased, 2 unaffected sisters did not have mutation, & affected sister has same mutation), ages 50 and 64, mod-severe ID & communication issues, one has hand tremor, aggression, and impulsivity | 2 | 682 |
| p.Ser136Trpfs*12 | c.407_408del | SETBP1-HD | de novo/not inherited | pathogenic | Jansen 2021:pt 6 | 1 | 136 | |
| p.Pro906Argfs*56 | c.2716_2717insGG | SETBP1-HD | de novo/not inherited | pathogenic | Jansen 2021:pt7 which is O'Roak 2012 12933.p1 | Autism, ID (from O'Roak - in a 10-year-old male with severe autism, adhd, excessive clumsiness and coordination problems, likely lof) | 1 | 906 |
| p.Lys693Profs*86 | c.2076_2092delinsC | SETBP1-HD | de novo/not inherited | pathogenic | Jansen 2021:pt 10, COM109 | 1 | 693 | |
| p.Lys152Trpfs*18 | c.453_454insTGGG | SETBP1-HD | de novo/not inherited | pathogenic | COM112, Jansen 2021:pt23 | 7 month old Male - Main symptom currently is Hypotonia | 1 | 152 |
| p.Arg615Ter | c.1843C>T | SETBP1-HD | de novo/not inherited | pathogenic | COM116, COM227 (inheritance unknown), COM247, COM268 | 4 | 615 | |
| p.Val1256Cysfs*28 | c.3765dup | SETBP1-HD | de novo/not inherited | pathogenic | Jansen 2021:pt8 | 1 | 1256 | |
| p.Gly1267Alafs*17 | c.3799_3800insC | SETBP1-HD | de novo/not inherited | pathogenic | Morgan et al 2021 pt13/COM110 | 1 | 1267 | |
| p.Tyr1040* | c.3120C>A | SETBP1-HD | de novo/not inherited | pathogenic | Morgan 2021:pt14, COM164 | 1 | 1040 | |
| p.(Ala113Leufs*94) | c.337delG | SETBP1-HD | de novo/not inherited | pathogenic | Morgan 2021:pt15, COM177 | 1 | 113 | |
| p.(Arg142Valfs*7) | c.422dup | SETBP1-HD | de novo/not inherited | pathogenic | Morgan 2021:pt22/COM122 | 1 | 142 | |
| p.(Gln135*) | c.403C>T | SETBP1-HD | de novo/not inherited | pathogenic | Morgan 2021:pt25 & COM245 | 2 | 135 | |
| p.Asp900Gly | c.2699A>G | SETBP1-related disorders | inherited | uncertain significance | COM123 | 1 | 900 | |
| p.Pro563fs | c.1677_1686dup | SETBP1-HD | don't know | likely pathogenic | CLINVAR: SCV001440011.1 | 1 | 563 | |
| p.Leu802fs | c.2406_2407delinsT | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: RCV001257737.2 | Severe intellectual disability | 1 | 802 |
| p.Met443fs | c.1329del | SETBP1-HD | don't know | pathogenic | Clinvar: SCV001820865.1 | 1 | 443 | |
| p.Ser791fs | c.2372_2387del | SETBP1-HD | don't know | pathogenic | Clinvar: SCV001762166.1 | Tall stature (yes) Intellectual disability (yes) Intention tremor (yes) Sagittal craniosynostosis (yes) Narrow palpebral fissure (yes) | 1 | 791 |
| p.Ser973Cys | c.2917A>T | SETBP1-related disorders | de novo/not inherited | uncertain significance | Anazi 2017/LOVD: 00361490 | Clinvar says VUS; however, LOVD states likely pathogenic due to the following reasons: AMG PS2,PM2,PP3 due to the stated paper | 1 | 973 |
| p.Ser214Lysfs*14 | c.640depA | SETBP1-HD | don't know | likely pathogenic | COM138 | 1 | 214 | |
| p.S167Vfs*40 | c.499de1 | SETBP1-HD | de novo/not inherited | pathogenic | COM140 | 1 | 167 | |
| p.Arg623Lysfs*7 | c.1878delG | SETBP1-HD | de novo/not inherited | likely pathogenic | COM64 | 1 | 623 | |
| p.(Gly15Alafs*49) | c.44del | SETBP1-HD | don't know | likely pathogenic | COM143, COM269, COM280 | inheritance (de novo, inherited, unknown) | 3 | 15 |
| p.Lys469_Met470insTer | c.1408del | SETBP1-HD | de novo/not inherited | pathogenic | Simons Searchlight/GenomeConnect/COM/Clinvar: RCV001265339.1, Ambry/Clinvar: RCV000623553.2 | Caesarian section (yes) Neonatal respiratory distress (yes) Poor suck (yes) Neonatal hypotonia (yes) Abnormality of vision (yes) Strabismus (yes) Generalized hypotonia (yes) Seizure precipitated by febrile infection (yes) Otitis media (yes) Failure to thrive (yes) / Global developmental delay (yes) Muscle weakness (yes) Muscular hypotonia (yes) Failure to thrive (yes) Narrow palpebral fissure (yes) Ptosis (yes) Movement disorder (yes) | 1 | 469 |
| 65MB deletion of SETBP1, PIK3C3, RIT2, SYT4, SLC14A2 and other genes | hg38 18q12.3 (39.823.856-42469.362) x1 | Proximal 18q- | de novo/not inherited | pathogenic | Cutrupi 2016 | http://www.thechild.it/archives/2016/1/index.php#8 (includes and references SETBP1 gene) | 1 | 9999 |
| Deletion of SETBP1, LOC647946, PIK3C3, RIT2, SYT4, RIT2 and other genes | 18q12.2q12.3(34576844_43015201)x1 | Proximal 18q- | de novo/not inherited | pathogenic | Jansen 2021 | 1 | 9999 | |
| Deletion of SETBP1, PIK3C3, RIT2, SYT4, SLC14A2 and other genes | 18q12.3q21.1(39600614_45460709)x1 | Proximal 18q- | de novo/not inherited | pathogenic | Jansen 2021 | 1 | 9999 | |
| Partial Deletion of SETBP1 | NC_000018.9:g.(?_42519449_42567840_?)del | SETBP1-HD | de novo/not inherited | pathogenic | Morgan 2021 | 1 | 9999 | |
| p.Val688fs | c.2061dupC | SETBP1-HD | de novo/not inherited | pathogenic | COM147 | 1 | 688 | |
| p.Pro855Ser | c.2563 C>T | SETBP1-related disorders | don't know | pathogenic | COM145 | 1 | 855 | |
| p.Ala1346Val | c.4037C>T | SETBP1-related disorders | don't know | uncertain significance | COM142 | 1 | 1346 | |
| p.S1332P | c.3994 T>C | SETBP1-related disorders | don't know | uncertain significance | COM239 | 1 | 1332 | |
| p.Glu639Gly | c.1916A>G | SETBP1-related disorders | don't know | uncertain significance | COM144 | 1 | 639 | |
| p.Gln211Argfs*132 | c.632del | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: 1302004/COM146 | 1 | 211 | |
| p.Lys425* | c.1273A>T | SETBP1-HD | de novo/not inherited | pathogenic | COM127/Kaspi (2022) | 1 | 425 | |
| p.Try1303* | c.3909T>A | SETBP1-HD | de novo/not inherited | likely pathogenic | COM126/ClinVar: RCV003148584.1 | 1 | 1303 | |
| p.Lys1413Glu | c.4237A>G | SETBP1-related disorders | de novo/not inherited | likely pathogenic | COM150 | in silico prediction analysis: deleterious mutation, likely pathogenic (ACMG) | 1 | 1413 |
| p.Trp827* | c.2480G>A | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: RCV001984593.4/COM151 | 1 | 827 | |
| p.(Glu545Aspfs*7) | c.1630_1636delinsAGAGA | SETBP1-HD | don't know | likely pathogenic | COM153 | 1 | 545 | |
| ~2MB Deletion - 18q12.3 Deletion including 5 OMIM genes, SETBP1,SYT4, LINC01601, MIR4319, RIT2 | hg19 18q12.3(18:40058331-42735067) | Proximal 18q- | don't know | pathogenic | COM155 | 1 | 9999 | |
| 18q12.3 deletion 183 kb includes SETBP1 | N/A | SETBP1-HD | de novo/not inherited | pathogenic | COM156 | 1 | 9999 | |
| p.(ser540fs) | c.1619del | SETBP1-HD | de novo/not inherited | pathogenic | COM157 | 1 | 540 | |
| p.(Ser763*) | c.2288_2289delinsG | SETBP1-HD | de novo/not inherited | pathogenic | COM158, DECIPHER: 454246 | Delayed speech and language development ; Downslanted palpebral fissures ; Hypertelorism ; Tented upper lip vermilion | 1 | 763 |
| p.P609S | c.1825 C>T | SETBP1-related disorders | don't know | uncertain significance | COM159 | 1 | 609 | |
| p.E286Rfs*47 | c.44dup | SETBP1-HD | don't know | pathogenic | COM160 | 1 | 286 | |
| 179kp deletion 18q12.3 contains part of SETBP1 & LINC01601 | hg19 18q12.3(42131941-42310517) | SETBP1-HD | don't know | pathogenic | COM161 | 1 | 9999 | |
| p.Asp138Profs*10 | c.408_409del | SETBP1-HD | don't know | pathogenic | COM129/Clinvar: 2117731 | 1 | 138 | |
| p.A549T | c.1645 G>A | SETBP1-related disorders | don't know | uncertain significance | COM128 | 1 | 549 | |
| p.Ser444Arg | c.1332C>G | SETBP1-related disorders | inherited | likely pathogenic | Wong et al 2022 | 1 | 444 | |
| p.Val657Ala | c.1970T>C | SETBP1-related disorders | inherited | likely pathogenic | Wong et al 2022 | 1 | 657 | |
| p.Thr962del | c.2885_2887del(CCA) | SETBP1-related disorders | de novo/not inherited | likely pathogenic | Wong et al 2022 (pre-print) & 2025; DECIPHER: 362041 (VUS) | in-frame deletion Phenotpye Wong: severe speech delay, inability to walk, tonic-clonic seizures, bilateral ptosis and had surgery to the right upper eyelid, left strabismus surgery, round face, Phenotype D: blepharophimosis, hypertelorism and a short nose with a bulbous tip / Phenotype: Blepharophimosis ; Cerebral atrophy ; Cleft palate ; Epicanthus inversus ; Hypoplasia of the corpus callosum ; Intellectual disability, severe ; Premature adrenarche ; Ptosis ; Scoliosis ; Seizure ; Short palpebral fissure ; Tented upper lip vermilion | 1 | 962 |
| p.Pro208Glnfs*135 | c.623del | SETBP1-HD | de novo/not inherited | pathogenic | COM162/Clinvar: 1805460 | 1 | 208 | |
| p.Tyr1263* | c.3788dup | SETBP1-HD | de novo/not inherited | pathogenic | COM166 | 1 | 1263 | |
| p.Lys106* | c.314_315dup | SETBP1-HD | don't know | pathogenic | COM167/clinvar: RCV002829123.3 | Submitted by Labcorp Genetics (formerly Invitae) and cited 2 SETBP1-HD publications | 1 | 106 |
| p.Ala1245fs | c.3731dup | SETBP1-HD | don't know | pathogenic | CLINVAR: 1320239 | Delayed fine motor development (present) , Motor delay (present) , Dolichocephaly (present) , Delayed speech and language development (present) , Intellectual disability (present) , Cerebellar ataxia (present) , Delayed gross motor development (present) , Macrocephalus (present) , Intellectual disability (present) , Generalized hypotonia (present) | 1 | 1245 |
| p.Asp1470fs | c.4409del | SETBP1-HD | don't know | uncertain significance | CLINVAR: VCV001307970.1 | Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation as the last 127 amino acids are lost and replaced with 21 incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge | 1 | 1470 |
| p.Arg1549fs | c.4645del | SETBP1-HD | don't know | uncertain significance | CLINVAR: VCV000452362.4 | GeneDX: Frameshift variant predicted to result in protein truncation as the last 48 amino acids are lost and replaced with 30incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge. | 1549 | |
| p.Lys1425Ter | c.4273A>T | SETBP1-HD | don't know | likely pathogenic | CLINVAR: RCV001808016.1 | 3billion: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10% (PVS1_S). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline Aphasia (present) , Global developmental delay (present) , Intellectual disability, moderate (present) | 1425 | |
| p.Gln1566Ter | c.4696C>T | SETBP1-HD | don't know | uncertain significance | CLINVAR: VCV001460993.1 | Invitae: This sequence change creates a premature translational stop signal (p.Gln1566*) in the SETBP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the SETBP1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SETBP1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. | 1566 | |
| p.Leu960Arg | c.2879T>G | SETBP1-related disorders | de novo/not inherited | likely pathogenic | CLINVAR: VCV001065614.2 and same as (Kaur et al 2024) | Submitter: Kasturba Medical College, Manipal, Manipal Academy of Higher Education Intellectual disability, autosomal dominant 29 (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo | 960 | |
| p.Ser893_Phe894insTer | c.2681_2682del | SETBP1-HD | don't know | pathogenic | Clinvar: RCV001823388.2 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge | 893 | |
| p.Val610ArgfsTer12 | c.1823_1824insC | SETBP1-HD | de novo/not inherited | pathogenic | DECIPHER: 388590 | Phenotype: Delayed speech and language development; Global developmental delay; Ichthyosis; Seizure; Short attention span; Short lingual frenulum; Speech apraxia | 610 | |
| p.Lys1136ArgfsTer2 | c.3403del | SETBP1-HD | inherited | likely pathogenic | DECIPHER: 306398. DECIPHER: 306397 | 306398: Phenotype: Broad chin; Broad face; Downslanted palpebral fissures; High palate; Long face; Severe global developmental delay, 306397: Phenotype: Delayed speech and language development; High myopia; High palate; Mandibular prognathia; Round face; Severe global developmental delay; Short toe | 2 | 1136 |
| p.Leu1035Ter | c.3104T>A | SETBP1-HD | de novo/not inherited | likely pathogenic | DECIPHER: 480287/COM185 (pathogenic c.3104dup) | Phenotype: Delayed speech and language development; Gait ataxia; Motor delay | 1035 | |
| p.Pro1539Ser | c.4615C>T | SETBP1-related disorders | don't know | likely pathogenic | COM169 | ASD - high functioning | 1539 | |
| 18q12.3 deletion 93 kb within SETBP1 | hg19 18q12.3(42,524,597_42,617,993)x1 | SETBP1-HD | inherited | pathogenic | Zhang 2022 | Child: At 2 years of age, the child underwent the Gessell examination, which indicated intellectual disability (intelligence quotient¼76) and language disorder (development quotient¼67). Parent: 28-year-old with intellectual disability and language disorder | 2 | 9999 |
| p.Val81Glyfs*33 | c.242_243del | SETBP1-HD | don't know | likely pathogenic | COM170/Clinvar: 2031944 | 1 | 81 | |
| p.Gly242AlafsTer101 | c.xxx | SETBP1-HD | de novo/not inherited | likely pathogenic | COM171 | 1 | 242 | |
| p.Ser867Asn | c.2600G>A | SETBP1-related disorders | don't know | likely pathogenic | COM174 | Individual does not have SGS. Symptoms align with SETBP1-HD. | 867 | |
| p.Glu858Lys | c.2572G>A | SETBP1-related disorders | don't know | likely pathogenic | COM173 | Inborn genetic diseases (yes) Neurologic (child onset) (yes) MR/ID/DD (yes) prominent forehead hypotonia (yes) | 6 | 858 |
| p. Phe177leufs*26 | c.528_540del | SETBP1-HD | de novo/not inherited | pathogenic | COM178 | 1 | 177 | |
| p.Ser1201Argfs*50 | c.3603_3606del | SETBP1-HD | de novo/not inherited | pathogenic | COM179 | 1 | 1201 | |
| p.Ala374fs | c.1119del | SETBP1-HD | inherited | pathogenic | COM184/Clinvar: 3254903 | 1 | 374 | |
| p.Ser247Thrfs*96 | c.740del | SETBP1-HD | don't know | pathogenic | COM187 | 1 | 247 | |
| p.S877R | c.2631C>A | SETBP1-related disorders | de novo/not inherited | likely pathogenic | Liu et al (2022) | She was found to have a motor and language development delay at 2 years old. The patient was born after 39 weeks with a normal gestation history. Facial features, including a prominent forehead, midface hypoplasia and protruding tongue. Brain MRI at 8 months of age showed delayed myelination of brain white matter and enlargement of the lateral ventricle, and the bilateral frontotemporal extracerebral space was significantly widened. Her karyotype analysis revealed normal results. | 877 | |
| 18q12.3(42202431_43059665)x1 | c.xxx | SETBP1-HD | don't know | pathogenic | COM188 | 9999 | ||
| p.D575Vfs*4 | c.1724_1727del | SETBP1-HD | de novo/not inherited | pathogenic | Wang 2023 pt 1 | The patient was referred for mental retardation, expressive and receptive language skills impairment and specific facial features (Fig. 1A, B). The patient was 156 cm in height and 49 kg in weigh. She was pregnant and the fetus was found abnormal lateral fissure in the brain, born the second child of healthy unrelated Chinese parents with one healthy brother after an uneventful term pregnancy. After birth, the patient can erect her head at 3 months, sit alone at the age of 6 months, and walk independently at 1 year and 5 months. Her language development was extremely backward so that she could only say two simple words: father and mother as of now. She also had the stereotyped movement of touching her lower lip. From the physical examination results, we noted her peculiar facial features: long face, high forehead, small palpebral fissures with ptosis, bilateral epicanthal folds, broad nasal tip, thin upper lip, fleshy lower lip and blush on both cheeks. No obvious abnormalities were found in routine blood test, routine coagulation test, cardiac color ultrasound and digestive system ultrasound. | 575 | |
| p.Asn876Lys | c.2628C>A | SETBP1-related disorders | de novo/not inherited | likely pathogenic | COM190 | 876 | ||
| p.His917ThrfsTer44 | c.2749del | SETBP1-HD | don't know | likely pathogenic | COM189 | 917 | ||
| p.Trp1242* | c.3725G>A | SETBP1-HD | don't know | likely pathogenic | COM192, Clinvar: SCV003921045.1 | Intellectual disability, autosomal dominant 29 Affected status: yes | 1242 | |
| p.Thr541Ile | c.1622C>T | SETBP1-related disorders | don't know | uncertain significance | COM193 | 1 | 541 | |
| p.Thr541Ile | c.1622C>T | SETBP1-related disorders | inherited | uncertain significance | COM194 | 1 | 541 | |
| p.H602Y | c.1804C>T | SETBP1-related disorders | de novo/not inherited | likely pathogenic | COM196 | 1 | 602 | |
| p.D757H | c.2269 G>C | SETBP1-related disorders | don't know | uncertain significance | COM197 | 1 | 757 | |
| p.E844K | c.2530 G>A | SETBP1-related disorders | don't know | uncertain significance | COM198 | 1 | 844 | |
| p.V235F | c.703 G>T | SETBP1-related disorders | don't know | uncertain significance | COM199 | 1 | 235 | |
| p.AIa408Thr | c.1222G>A | SETBP1-related disorders | don't know | uncertain significance | COM200 | 1 | 408 | |
| p.Pro855Thr | c.2563C>A | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM201 | 1 | 855 | |
| p.Asp316TrpfsTer28 | c.942_943insGT | SETBP1-HD | inherited | pathogenic | Wang, Le etc al 2023 | Proband was a woman aged 27 with moderate ID and language delay. She is the third child of non-consanguineous parents. Her 29-year-old sister had the same symptoms, while her 31-year-old sister was healthy and had a normal cognition. Her mother also had the same mutation and normal MRI. Proband, middle sister and mother presented with the same symptoms. "Novel SETBP1 mutation in a Chinese family with intellectual disability" | 3 | 316 |
| 6.21-Mb deletion at 18q12.3q21.1 which includes many genes including RIT2, SYT4, SETBP1, SLC14A2, EPG5, KATNAL2 and other genes | hg19 18q12.3q21.1(39747201-45955757) | Proximal 18q- | de novo/not inherited | pathogenic | Wang, R et al 2018 (Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China) | Case BY935 is a six-year-and-one-month-old female with ID and facial dysmorphism | 1 | 9999 |
| p.Gly1172Val | c.3515G>T | SETBP1-related disorders | don't know | uncertain significance | Alagöz, M et al 2019 | Atypical autistic behavior, delayed speech and language development, and intellectual disability. The eight-year-old patient has no history of seizures and no consanguineous marriage in his family. | 1 | 1172 |
| p.Ala290Ser | c. 868G>T | SETBP1-related disorders | don't know | uncertain significance | COM203, LOVD3 ID: 00316194 | 2 | 290 | |
| p.S1296Efs*4 | c.3884dup | SETBP1-HD | de novo/not inherited | pathogenic | COM204 | 1 | 1296 | |
| p.S269Rfs*9 | c.802_807delinsG | SETBP1-HD | don't know | pathogenic | Personal or Family Member's Genetic Report | genotype-phenotype matching . Could you please emphasize on your website that SETBP1-HD and SETBP-1 related disorder are different entities? Thanks | 269 | |
| p.S869G | c.2605A > G | Schinzel-Giedion syndrome (classic) | de novo/not inherited | pathogenic | Yang 2022 | 1 | 869 | |
| 18q12.3(chr18:42407013_42453303)x1 | c.xxx | SETBP1-HD | don't know | likely pathogenic | COM209 | 1 | 9999 | |
| p.Leu960Pro | c.2879T>C | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM210 | 1 | 960 | |
| p.Arg421LysfsTer5 | c.1261dup | SETBP1-HD | don't know | likely pathogenic | COM211, COM303 | 2 | 421 | |
| p.Ser344Aspfs*18 | c.1030_1034del | SETBP1-HD | de novo/not inherited | likely pathogenic | COM212/Clinvar: 2029311 | 1 | 344 | |
| p.Gln766* | c.2296C>T | SETBP1-HD | don't know | pathogenic | COM215 | 1 | 766 | |
| p.Pro1526fs | c.4575_4578delACCG | SETBP1-HD | de novo/not inherited | likely pathogenic | COM216 | 1 | 1526 | |
| p.Ala694fs | c.2083dupC | SETBP1-HD | don't know | pathogenic | COM216 | 1 | 694 | |
| p.Gln965_Phe967del | c.2893_2910del | SETBP1-HD | don't know | likely pathogenic | COM217 | 1 | 9999 | |
| SETBP1 Partial Deletion (Exon 2) | c.333_486+171del | SETBP1-HD | don't know | likely pathogenic | COM218 | 1 | 9999 | |
| p.Arg914fs | c.2740delC | SETBP1-HD | don't know | pathogenic | COM206 | 1 | 914 | |
| p.Ser932AlafsTer29 | c.2794del | SETBP1-HD | de novo/not inherited | pathogenic | COM219 | 1 | 932 | |
| arr[hg19] 18q12.3(42,453,211–42,988,420)x1 | N/A | SETBP1-HD | don't know | pathogenic | Chaves 2024, #667 | ASD | 1 | 9999 |
| p.S1590C | c.4768A>T | SETBP1-related disorders | don't know | uncertain significance | COM221 | 1 | 1590 | |
| p.Leu206* | c.6171>A | SETBP1-HD | de novo/not inherited | pathogenic | COM241, COM242 (siblings)/Clinvar: RCV003544503.2RCV003544503.2 | Submitted by Labcorp Genetics (formerly Invitae) and cited 2 SETBP1-HD publications | 2 | 206 |
| p.R1324* | c.3970A>T | SETBP1-HD | don't know | pathogenic | COM223 | 1 | 1324 | |
| p.Gln965* | c.2893C>T | SETBP1-HD | don't know | likely pathogenic | COM224 | 1 | 965 | |
| p.His1156Glnfs*39 | c.3464_3465ins235 | SETBP1-HD | don't know | pathogenic | Personal or Family Member's Genetic Report | 1 | 1156 | |
| p.Thr273Serfs*70 | c.818del | SETBP1-HD | de novo/not inherited | pathogenic | COM228 | 1 | 273 | |
| p.GIn782* | c.2344C>T | SETBP1-HD | de novo/not inherited | pathogenic | COM230 | 1 | 782 | |
| p.Ser241Trpfs*14 | c.722_723del | SETBP1-HD | de novo/not inherited | pathogenic | COM231 | 1 | 241 | |
| p.T1028Kfs*78 | c.3083_3090del | SETBP1-HD | de novo/not inherited | pathogenic | COM233 | 1 | 1028 | |
| 18Q Deletion - start PIK3C3 to end: KATNAL2 and includes SETBP1 | hg19 18q12.3q21.3(37359733-44519456)x1 | Proximal 18q- | don't know | pathogenic | COM234 | 1 | 9999 | |
| p.Asn119Glufs*10 | c.350dup | SETBP1-HD | don't know | likely pathogenic | COM236 | 1 | 119 | |
| p.Ser1187Thrfs*4 | c.3560del | SETBP1-HD | don't know | pathogenic | COM237 | 1 | 1187 | |
| p.Glu487fs | c.1459del | SETBP1-HD | don't know | pathogenic | Clinvar: 2697692 | Submitted by Labcorp Genetics (formerly Invitae) and cited 2 SETBP1-HD publications | 1 | 487 |
| p.Tyr562fs | c.1684del | SETBP1-HD | don't know | pathogenic | Clinvar: 2012855 | Submitted by Labcorp Genetics (formerly Invitae) and cited 2 SETBP1-HD publications | 1 | 562 |
| p.Pro696fs | c.2087del | SETBP1-HD | don't know | pathogenic | Clinvar: SCV004103588.1 | Submitted by PreventionGenetics, part of Exact Sciences and cited 2 SETBP1-HD publications | 1 | 696 |
| p.Gly728fs | c.2183del | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: RCV004771590.1 | Submitted by Institute of Immunology and Genetics Kaiserslautern. Global developmental delay (present) | 1 | 728 |
| p.Leu779fs | c.2334_2515del | SETBP1-HD | don't know | pathogenic | clinvar: RCV004547089.6 | Submitted by CeGaT Center for Human Genetics Tuebingen | 1 | 779 |
| p.Ser780fs | c.2338del | SETBP1-HD | don't know | likely pathogenic | Clinvar: RCV004598352.1 | Submitted by MVZ Medizinische Genetik Mainz - High palate (present) , Low-set ears (present) , Downslanted palpebral fissures (present) , Atypical behavior (present) , Aggressive behavior (present) , Delayed speech and language development (present) , Global developmental delay (present) , Motor delay (present) , High, narrow palate (present) , Few cafe-au-lait spots (present) , Narrow naris (present) , Prominent forehead (present) , Microphakia (present) , Finger clinodactyly (present) | 1 | 780 |
| p.His921fs | c.2762del | SETBP1-HD | don't know | pathogenic | Clinvar: RCV004698369.1 | Submitted by Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen. | 1 | 921 |
| p.His938fs | c.2812del | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: RCV003326179.2 | Submitted by Pediatric Department, Xiangya Hospital, Central South University. | 1 | 938 |
| p.Leu960fs | c.2878_2879delinsG | SETBP1-HD | don't know | likely pathogenic | Clinvar: RCV001783730.4 | Submitted by Revvity Omics, Revvity. | 1 | 960 |
| p.Gly64_Ser65insGlyGlyTer | c.176_191dup | SETBP1-HD | don't know | pathogenic | Clinvar: RCV003229199.1 | Sumbitted by GeneDx with no additional details. | 1 | 64 |
| p.Trp80Ter | c.239G>A | SETBP1-HD | don't know | likely pathogenic | clinvar: RCV004771608.1 | Submitted by Institute of Immunology and Genetics Kaiserslautern | 1 | 80 |
| p.Trp80Ter | c.240G>A | SETBP1-HD | don't know | pathogenic | clinvar: RCV003709073.2 | Submitted by Labcorp Genetics (formerly Invitae) and cited 2 SETBP1-HD publications | 1 | 80 |
| p.Gln312Ter | c.934C>T | SETBP1-HD | don't know | likely pathogenic | ClinVar: RCV002224749.1 | Submitted by AiLife Diagnostics, AiLife Diagnostics | 1 | 312 |
| p.Ser1443Ter | c.4328C>G | SETBP1-HD | don't know | likely pathogenic | ClinVar: RCV003444527.1 | Submitted by Zotz-Klimas Genetics Lab, MVZ Zotz Klimas | 1 | 1443 |
| p.Glu1188Ter | c.3562G>T | SETBP1-HD | don't know | pathogenic | clinVar: RCV004778186.1/ | Submitted by GeneDx | 1 | 1188 |
| p.Val387_Ser388insTer | c.1160_1161insTT | SETBP1-HD | don't know | pathogenic | Clinvar: RCV003550026.2 | Submitted by Labcorp Genetics (formerly Invitae), Labcorp | 1 | 387 |
| p.G101* | c.301G>T | SETBP1-HD | de novo/not inherited | pathogenic | COM243 | individual also has other likely pathogenic variant | 1 | 101 |
| p.D375* | C.1123_1124del | SETBP1-HD | de novo/not inherited | pathogenic | COM244 | 1 | 375 | |
| p.S275lfs*68 | c.824del | SETBP1-HD | don't know | pathogenic | COM248 | 1 | 275 | |
| p.Arg112fs | c.334del | SETBP1-HD | don't know | pathogenic | Clinvar: SCV005397071.2 | Comment: Criteria applied: PVS1,PS2_MOD,PM2 Clinical Features: Autistic behavior (present) , Intellectual disability, moderate (present) , Global developmental delay (present) Sex: female | 1 | 112 |
| p.Asn147fs | c.440dup | SETBP1-HD | don't know | pathogenic | Clinvar: SCV003228488.2 | This sequence change creates a premature translational stop signal (p.Asn147Lysfs*2) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. | 1 | 147 |
| p.Ser172fs | c.514dup | SETBP1-HD | don't know | pathogenic | Clinvar: SCV003216387.2 | This sequence change creates a premature translational stop signal (p.Ser172Lysfs*2) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. | 1 | 172 |
| p.Arg531fs | c.1593del | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: SCV005420330.1 | male | 1 | 531 |
| p.Gly653fs | c.1955_1956dup | SETBP1-HD | don't know | likely pathogenic | Clinvar: SCV004013743.1 | Clinical Features: Intellectual disability, mild (present) , Autistic behavior (present) , Tetralogy of Fallot (present) , Neurodevelopmental abnormality (present) The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. | 1 | 653 |
| p.Asn913fs | c.2738dup | SETBP1-HD | don't know | pathogenic | Clinvar: SCV004366791.1 | This sequence change creates a premature translational stop signal (p.Asn913Lysfs*38) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. | 1 | 913 |
| p.Ala1071fs | c.3211del | SETBP1-HD | don't know | pathogenic | Clinvar: SCV005423537.1 | Variant summary: SETBP1 c.3211delG (p.Ala1071LeufsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. | 1 | 1071 |
| p.Asp119fs | c.3580_3583del | SETBP1-HD | de novo/not inherited | pathogenic | COM253 | 1 | 119 | |
| p.Ser877Phefs*2 | c.2629_2633del | SETBP1-HD | don't know | pathogenic | COM254 | 877 | ||
| SETBP1 340kb deletion | chr18:42281312-42643731 | SETBP1-HD | don't know | pathogenic | COM255 | 1 | 9999 | |
| p.(Glu850Asp) | c.2550A>T | SETBP1-related disorders | don't know | uncertain significance | COM182 | 1 | 850 | |
| 6.2 MB deletion including SETBP1 | hg19 18q12.3-21.1(42033966-48246952) | Proximal 18q- | de novo/not inherited | pathogenic | COM258 | 1 | 6 | |
| p.(Ser10Tyr) | c.29c>a | SETBP1-related disorders | don't know | uncertain significance | COM260 | 1 | 10 | |
| p.(C308*) | c.923_924delinsAA | SETBP1-HD | de novo/not inherited | pathogenic | COM261 | 1 | 308 | |
| p.N676Kfs*31 | c.2027dup | SETBP1-HD | unknown (not maternally inherited) | pathogenic | COM262 | 1 | 676 | |
| SETBP1 48kb deletion | chr18:42519449_42567640 | SETBP1-HD | don't know | pathogenic | COM264 | 1 | 9999 | |
| SETBP1 deletion | chr18:42260850_42618621 | SETBP1-HD | don't know | pathogenic | COM266 | 1 | 9999 | |
| p.(Q634*) | c.1900 C>T | SETBP1-HD | don't know | pathogenic | COM267 | 1 | 634 | |
| p.(Ser567Cys) & p.(Ser857Thr) | c.1700C>G & c.2570G>C | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM270 | 1 | 567 | |
| p.Ala528Thr | c.1582G>A | SETBP1-related disorders | inherited | uncertain significance | COM271 | 1 | 528 | |
| p.Q1000Sfs*15 | c. 2995_2996dup | SETBP1-HD | de novo/not inherited | pathogenic | COM272 & COM273 | 2 | 1000 | |
| p.Leu802* | c.2405del | SETBP1-HD | de novo/not inherited | pathogenic | COM274 | 1 | 802 | |
| SETBP1 5mb deletion | hg19 18q12.3-18q21.1(39836056-44849232) | Proximal 18q- | inherited | pathogenic | COM276, COM277 | maternally inherited, Unknown for other | 2 | 46027 |
| p Pro855Leu | c.2564C>T | SETBP1-related disorders | don't know | likely pathogenic | COM278 | 1 | 855 | |
| p.Tyr571Serfs*9 | c.1712del | SETBP1-HD | de novo/not inherited | likely pathogenic | COM279 | 1 | 571 | |
| p.Arg551Cys | c.1651C>T | SETBP1-related disorders | de novo/not inherited | pathogenic | COM283 | 1 | 551 | |
| p.Arg1296GlyfsTer20 | c.3886dup | SETBP1-HD | de novo/not inherited | pathogenic | COM284 | 1 | 1296 | |
| p.His841Pro | c.xxxxx | SETBP1-related disorders | don't know | uncertain significance | COM285 | 1 | 841 | |
| p.Gln1213Ter | c.3637C>T | SETBP1-HD | de novo/not inherited | pathogenic | COM286 | 1 | 1213 | |
| p.Glu697fs | c.2087dup | SETBP1-HD | de novo/not inherited | pathogenic | Clinvar: SCV002767006 | 1 | 697 | |
| p.Lys1220Arg | c.3659A>G | SETBP1-related disorders | de novo/not inherited | uncertain significance | COM282 | 1 | 1220 | |
| p.S877G | c.2629 A>G | SETBP1-related disorders | de novo/not inherited | pathogenic | COM287 | 1 | 877 | |
| p.Trp827* | c.2481G>A | SETBP1-HD | de novo/not inherited | pathogenic | COM288 | 1 | 827 | |
| p.Leu768Pro | c.2303T>C | SETBP1-related disorders | inherited from father | uncertain significance | COM290 | 1 | 768 | |
| SETBP1 6.3MB Deletion | hg19 18q12.3-18q21.1 | Proximal 18q- | de novo/not inherited | pathogenic | COM289 | 1 | 9999 | |
| p.Pro185Glyfs*23 | c.550_551dup | SETBP1-HD | de novo/not inherited | pathogenic | COM293 | 1 | 185 | |
| p.Tyr193ter | c.587_579del | SETBP1-HD | de novo/not inherited | pathogenic | COM294 | 1 | 193 | |
| p.Gly203Valfs*4 | c.607delG | SETBP1-HD | de novo/not inherited | pathogenic | Wan et al (2023) | Liu 2023: Case 1: Male, 5 years old, Main complaint: limited speech, Good comprehension, could follow daily instructions, used gestures to communicate, Socially engaged, no stereotyped behavior, no seizures, Developmental milestones mildly delayed, Wechsler IQ: Verbal IQ 44, Performance IQ 50, Full IQ 44, Brain MRI and video EEG: normal | 1 | 203 |
| p.S707N | c.2120 G>A | SETBP1-related disorders | don't know | uncertain significance | COM295 | 1 | 707 | |
| p.pro199Thrfs*10 | c.594dupA | SETBP1-HD | de novo/not inherited | likely pathogenic | COM296 | 1 | 199 | |
| p.Ala774Glu | c.2321C>A | SETBP1-related disorders | inherited | uncertain significance | siblings (COM295, COM296) & parent COM297 (inheritance unknown) | 3 | 774 | |
| p.L1278Wfs*7 | c.3832del | SETBP1-HD | don't know | pathogenic | COM301 | 1 | 1278 | |
| p.Pro855Leufs*2 | c.2564del | SETBP1-HD | don't know | pathogenic | COM302 | 1 | 855 | |
| p.L1278Wfs*7 | c.3832del | SETBP1-HD | don't know | pathogenic | COM301 | 1 | 1278 |