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Examples Gene: MT-ND1, POLG, Region: M:1-1000 Variant: m.8993T>G, 1:g.10042757T>C rs3888511 MSCV_0000006, ClinVar: RCV000000015, Disease: Leigh syndrome, Phenotype: Retinopathy

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Disease Browser
Parent Node: Abnormalities, Multiple (D000015)
Parent Node: Craniofacial Abnormalities (D019465)
Parent Node: Genetic Diseases, Inborn (D030342)
..Starting node ..Costello Syndrome (D056685)
Child Nodes:
Sister Nodes:
..ACTH Deficiency, Isolated (C562707)
..Adrenal Hyperplasia, Congenital (D000312) 12
..Adrenocortical Hypofunction, Chronic Primary Congenital (C562711)
..Alagille Syndrome (D016738)
..alpha 1-Antitrypsin Deficiency (D019896) 1
..Alpha-2-Deficient Collagen Disease (C565963)
..Anemia, Hemolytic, Congenital (D000745) 68
..Anemia, Hypoplastic, Congenital (D029502) 27
..Angioedemas, Hereditary (D054179) 2
..Ataxia Telangiectasia (D001260) 6
..Atrial Standstill (C563984)
..Autoimmune Lymphoproliferative Syndrome (D056735) 5
..Blood Coagulation Disorders, Inherited (D025861) 70
..Brugada Syndrome (D053840) 9
..CADASIL (D046589) 1
..Camurati-Engelmann Syndrome (D003966) 4
..Cardiomyopathy, Hypertrophic, Familial (D024741) 15
..Cerebral Palsy, Ataxic, Autosomal Recessive (C562856)
..CHARGE Syndrome (D058747)
..Cherubism (D002636) 2
..Chromosome Disorders (D025063) 160
..Cirrhosis, Familial (C566123)
..Complement Factor I Deficiency (C572568)
..Corticosteroid-Binding Globulin Deficiency (C565152)
..Costello Syndrome (D056685)
..Cryoglobulinemia, Familial Mixed (C565141)
..Cystic Fibrosis (D003550) 4
..Donohue Syndrome (D056731) 1
..Dwarfism (D004392) 155
..Epistaxis, Hereditary (C562751)
..Eye Diseases, Hereditary (D015785) 373
..Frasier Syndrome (D052159)
..Genetic Diseases, X-Linked (D040181) 412
..Genetic Diseases, Y-Linked (D050174) 5
..Hajdu-Cheney Syndrome (D031845) 1
..Hemoglobinopathies (D006453) 23
..Hepatic Fibrosis, Congenital (C562378)
..Hereditary Autoinflammatory Diseases (D056660) 10
..Hereditary Myopathy with Early Respiratory Failure (C566343)
..Heredodegenerative Disorders, Nervous System (D020271) 543
..Histiocytosis, Familial Lipochrome (C562738)
..Hyper-IgM Immunodeficiency Syndrome (D053306) 3
..Hyperthyroxinemia, Familial Dysalbuminemic (D050010) 1
..Interstitial Pneumonitis, Desquamative, Familial (C562470)
..Kallmann Syndrome (D017436) 9
..Kartagener Syndrome (D007619) 6
..Lennox Gastaut Syndrome (D065768) 1
..Loeys-Dietz Syndrome (D055947) 5
..Marfan Syndrome (D008382) 9
..Metabolism, Inborn Errors (D008661) 886
..Muscular Dystrophies (D009136) 117
..Myasthenic Syndromes, Congenital (D020294) 15
..Nail-Patella Syndrome (D009261) 1
..Neoplastic Syndromes, Hereditary (D009386) 111
..Neutropenia, Nonimmune Chronic Idiopathic, Adult (C564320)
..Osteoarthropathy, Primary Hypertrophic (D010004) 2
..Osteogenesis Imperfecta (D010013) 27
..Pain Insensitivity, Congenital (D000699) 2
..Parotidomegaly, Hereditary Bilateral (C566821)
..Pelger-Huet Anomaly (D010381)
..Platelet Glycoprotein IV Deficiency (C564245)
..Polycystic Kidney, Autosomal Recessive (D017044) 3
..Prolactin Deficiency, Isolated (C562708)
..Pulmonary Alveolar Microlithiasis (C562405)
..Pycnodysostosis (D058631)
..Rh Deficiency Syndrome (C562717)
..Skin Diseases, Genetic (D012873) 462
..Weill-Marchesani Syndrome (D056846)
..Werner Syndrome (D014898) 1
..Yellow Nail Syndrome (D056684) 1
Human Disease MESH is developed by UMLS. Further data from MedGen, OMIM, CTD

Term ID:

2786

Name:

Costello Syndrome

Definition:

Rare congenital disorder with multiple anomalies including: characteristic dysmorphic craniofacial features, musculoskeletal abnormalities, neurocognitive delay, and high prevalence of cancer. Germline mutations in H-Ras protein can cause Costello syndrome. Costello syndrome shows early phenotypic overlap with other disorders that involve MAP KINASE SIGNALING SYSTEM (e.g., NOONAN SYNDROME and cardiofaciocutaneous syndrome).

Alternative IDs:

OMIM:218040

ParentIDs:

MESH:D000015|MESH:D019465|MESH:D030342

TreeNumbers:

C05.660.207.219 |C16.131.077.256 |C16.320.185

Synonyms:

Slim Mappings:

Congenital abnormality|Genetic disease (inborn)|Musculoskeletal disease

Reference:

MedGen: D056685
MeSH: D056685
OMIM: 218040;

Genes: HRAS;

Phenotypes

1	HP:0000006	Autosomal dominant inheritance
2	HP:0000956	Acanthosis nigricans
3	HP:0001771	Achilles tendon contracture
4	HP:0000463	Anteverted nares
5	HP:0007099	Arnold-Chiari type I malformation
6	HP:0011675	Arrhythmia
7	HP:0001631	Atrial septal defect
8	HP:0001552	Barrel-shaped chest
9	HP:0002862	Bladder carcinoma
10	HP:0002780	Bronchomalacia
11	HP:0002059	Cerebral atrophy
12	HP:0000280	Coarse facial features
13	HP:0001598	Concave nail
14	HP:0002212	Curly hair
15	HP:0006191	Deep palmar crease
16	HP:0001869	Deep plantar creases
17	HP:0001814	Deep-set nails
18	HP:0005280	Depressed nasal bridge
19	HP:0000494	Downslanted palpebral fissures
20	HP:0012081	Enlarged cerebellum
21	HP:0000286	Epicanthus
22	HP:0001508	Failure to thrive
23	HP:0001808	Fragile nails
24	HP:0000293	Full cheeks
25	HP:0001263	Global developmental delay
26	HP:0000218	High palate
27	HP:0001609	Hoarse voice
28	HP:0000238	Hydrocephalus
29	HP:0001187	Hyperextensibility of the finger joints
30	HP:0000953	Hyperpigmentation of the skin
31	HP:0000316	Hypertelorism
32	HP:0001639	Hypertrophic cardiomyopathy
33	HP:0001943	Hypoglycemia
34	HP:0001249	Intellectual disability
35	HP:0002996	Limited elbow movement
36	HP:0000369	Low-set ears
37	HP:0000256	Macrocephaly
38	HP:0000158	Macroglossia
39	HP:0000347	Micrognathia
40	HP:0001634	Mitral valve prolapse
41	HP:0003764	Nevus
42	HP:0002870	Obstructive sleep apnea
43	HP:0001548	Overgrowth
44	HP:0000768	Pectus carinatum
45	HP:0002107	Pneumothorax
46	HP:0000307	Pointed chin
47	HP:0001561	Polyhydramnios
48	HP:0002033	Poor suck
49	HP:0000358	Posteriorly rotated ears
50	HP:0001622	Premature birth
51	HP:0000508	Ptosis
52	HP:0001642	Pulmonic stenosis
53	HP:0002021	Pyloric stenosis
54	HP:0005989	Redundant neck skin
55	HP:0000083	Renal insufficiency	HP:0040283
56	HP:0002878	Respiratory failure
57	HP:0002093	Respiratory insufficiency
58	HP:0002859	Rhabdomyosarcoma
59	HP:0000470	Short neck
60	HP:0004322	Short stature
61	HP:0008070	Sparse hair
62	HP:0003745	Sporadic
63	HP:0000486	Strabismus
64	HP:0001699	Sudden death
65	HP:0001762	Talipes equinovarus
66	HP:0000179	Thick lower lip vermilion
67	HP:0001816	Thin nail
68	HP:0002779	Tracheomalacia
69	HP:0001629	Ventricular septal defect
70	HP:0002119	Ventriculomegaly
71	HP:0009588	Vestibular Schwannoma
72	HP:0000465	Webbed neck
73	HP:0000260	Wide anterior fontanel

Disease Causing ClinVar Variants

Variation_Name	GeneID	GeneSymbol	ClinicalSignificance	dbSNP	RCVaccession	TestedInGTR	PhenotypeIDs	Chromosome	Start	Stop	HGVS_c	HGVS_p	HGVS_g	OtherIDs	Disease_ClinVar
NM_005343.3(HRAS):c.437C>T (p.Ala146Val)	-1	-	Likely pathogenic;Pathogenic	121917759	RCV000013445;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533466	533466	NM_005343.3:c.437C>T	NP_005334.1:p.Ala146Val	NC_000011.9:g.533466G>A	OMIM Allelic Variant:190020.0012	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.436G>A (p.Ala146Thr)	-1	-	Pathogenic	104894231	RCV000013441;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533467	533467	NM_005343.3:c.436G>A	NP_005334.1:p.Ala146Thr	NC_000011.9:g.533467C>T	OMIM Allelic Variant:190020.0008	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.350A>G (p.Lys117Arg)	-1	-	Pathogenic	104894227	RCV000013439;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533553	533553	NM_005343.3:c.350A>G	NP_005334.1:p.Lys117Arg	NC_000011.9:g.533553T>C	OMIM Allelic Variant:190020.0006	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.187_207dup21 (p.Asp69_Gln70insGluTyrSerAlaMetArgAsp)	-1	-	Pathogenic	587777239	RCV000106320;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533849	533869	NM_005343.3:c.187_207dup21	NP_005334.1:p.Asp69_Gln70insGluTyrSerAlaMetArgAsp		OMIM Allelic Variant:190020.0018	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.175_176delGCinsCT (p.Ala59Leu)	-1	-	Likely pathogenic	727504747	RCV000156047;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533880	533881	NM_005343.3:c.175_176delGCinsCT	NP_005334.1:p.Ala59Leu	NC_000011.9:g.533880_533881delinsAG	-	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.175G>A (p.Ala59Thr)	-1	-	Likely pathogenic;Pathogenic	727503093	RCV000150835; RCV000150834; RCV000157916;	N	MedGen:C0007131,SNOMED CT:254637007; MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:CN166718	11	533881	533881	NM_005343.3:c.175G>A	NP_005334.1:p.Ala59Thr		-	C0587248 218040 Costello syndrome; C0007131 Non-small cell lung cancer; CN166718 Rasopathy
NM_176795.4(HRAS):c.173C>T (p.Thr58Ile)	-1	-	Pathogenic	121917758	RCV000013444;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	533883	533883	NM_176795.4:c.173C>T	NP_789765.1:p.Thr58Ile	NC_000011.9:g.533883G>A	OMIM Allelic Variant:190020.0011	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.110_111+1dupAGG	-1	-	Pathogenic	398122808	RCV000022797;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	534211	534213	NM_005343.3:c.110_111+1dupAGG		NC_000011.9:g.534211_534213dupCCT	OMIM Allelic Variant:190020.0015	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.108_110dupAGA (p.Glu37_Asp38insGlu)	-1	-	Pathogenic	398122809	RCV000022798;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	534213	534215	NM_005343.3:c.108_110dupAGA	NP_005334.1:p.Glu37_Asp38insGlu	NC_000011.9:g.534213_534215dupTCT	OMIM Allelic Variant:190020.0016	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.64C>A (p.Gln22Lys)	-1	-	Likely pathogenic;Pathogenic	121917757	RCV000143898; RCV000013443; RCV000157915;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C1968782; MedGen:CN166718	11	534259	534259	NM_005343.3:c.64C>A	NP_005334.1:p.Gln22Lys		OMIM Allelic Variant:190020.0010	C0587248 218040 Costello syndrome; C1968782 Myopathy, congenital, with excess of muscle spindles; CN166718 Rasopathy
NM_005343.3(HRAS):c.38G>A (p.Gly13Asp)	-1	-	Pathogenic	104894226	RCV000013438; RCV000157913;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:CN166718	11	534285	534285	NM_005343.3:c.38G>A	NP_005334.1:p.Gly13Asp		OMIM Allelic Variant:190020.0005	C0587248 218040 Costello syndrome; CN166718 Rasopathy
NM_005343.3(HRAS):c.37G>T (p.Gly13Cys)	-1	-	Pathogenic	104894228	RCV000013440; RCV000149831; RCV000207504;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:CN166718; MedGen:CN235269	11	534286	534286	NM_005343.3:c.37G>T	NP_005334.1:p.Gly13Cys		OMIM Allelic Variant:190020.0007	C0587248 218040 Costello syndrome; CN235269 none provided; CN166718 Rasopathy
NM_005343.3(HRAS):c.35_36delGCinsAA (p.Gly12Glu)	-1	-	Likely pathogenic	727503094	RCV000150836;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	534287	534288	NM_005343.3:c.35_36delGCinsAA	NP_005334.1:p.Gly12Glu		-	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.36C>T (p.Gly12=)	-1	-	Uncertain significance	727504424	RCV000207496;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008	11	534287	534287	NM_005343.3:c.36C>T	NP_005334.1:p.Gly12=		-	C0587248 218040 Costello syndrome
NM_005343.3(HRAS):c.35G>T (p.Gly12Val)	-1	-	Pathogenic	104894230	RCV000013432; RCV000013433; RCV000032850; RCV000013431; RCV000157912;	N	MedGen:C0005684,OMIM:109800,SNOMED CT:399326009; MedGen:C0334082,OMIM:162900,ORPHA:35125,SNOMED CT:25201003; MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C1968782; MedGen:CN221809	11	534288	534288	NM_005343.3:c.35G>T	NP_005334.1:p.Gly12Val		OMIM Allelic Variant:190020.0001	C0587248 218040 Costello syndrome; C0334082 162900 Epidermal nevus; C0005684 109800 Malignant tumor of urinary bladder; C1838979 252010 Mitochondrial complex I deficiency; C1968782 Myopathy, congenital, with excess of muscle spindles; CN221809 not prov
NM_005343.3(HRAS):c.35G>C (p.Gly12Ala)	-1	-	Pathogenic	104894230	RCV000013437; RCV000157911; RCV000207503;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:CN166718; MedGen:CN235269	11	534288	534288	NM_005343.3:c.35G>C	NP_005334.1:p.Gly12Ala		OMIM Allelic Variant:190020.0004	C0587248 218040 Costello syndrome; CN235269 none provided; CN166718 Rasopathy
NM_005343.3(HRAS):c.35G>A (p.Gly12Asp)	-1	-	Pathogenic	104894230	RCV000038460; RCV000013446; RCV000029210; RCV000149830; RCV000212496;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C0853032; MedGen:C4016398; MedGen:CN166718; MedGen:CN221809	11	534288	534288	NM_005343.3:c.35G>A	NP_005334.1:p.Gly12Asp		OMIM Allelic Variant:190020.0013	C0587248 218040 Costello syndrome; C4016398 Costello syndrome, severe; C0853032 Nevus sebaceous; CN221809 not provided; CN166718 Rasopathy
NM_005343.3(HRAS):c.34G>A (p.Gly12Ser)	-1	-	Pathogenic	104894229	RCV000013435; RCV000013436; RCV000022796; RCV000029209; RCV000149828; RCV000081295; RCV000173004;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C0853032; MedGen:C1968782; MedGen:C3277679; MedGen:CN166718; MedGen:CN221809; MedGen:CN231320	11	534289	534289	NM_005343.3:c.34G>A	NP_005334.1:p.Gly12Ser		HGMD:CM053283,OMIM Allelic Variant:190020.0003	C0587248 218040 Costello syndrome; C3277679 Epidermal nevus with urothelial cancer, somatic; C1968782 Myopathy, congenital, with excess of muscle spindles; C0853032 Nevus sebaceous; CN231320 Nevus, woolly hair; CN221809 not provided; CN166718 Rasop
NM_005343.3(HRAS):c.34G>T (p.Gly12Cys)	-1	-	Pathogenic	104894229	RCV000013447; RCV000032851; RCV000029211; RCV000149829; RCV000212495;	N	MedGen:C0334082,OMIM:162900,ORPHA:35125,SNOMED CT:25201003; MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C0853032; MedGen:CN166718; MedGen:CN221809	11	534289	534289	NM_005343.3:c.34G>T	NP_005334.1:p.Gly12Cys		OMIM Allelic Variant:190020.0014	C0587248 218040 Costello syndrome; C0334082 162900 Epidermal nevus; C1838979 252010 Mitochondrial complex I deficiency; C0853032 Nevus sebaceous; CN221809 not provided; CN166718 Rasopathy
NM_000364.3(TNNT2):c.853C>T (p.Arg285Cys)	7139	TNNT2	Likely pathogenic;Pathogenic;Uncertain significance	121964857	RCV000148898; RCV000013222; RCV000157540; RCV000162331; RCV000203739; RCV000159322; RCV000036622;	N	MedGen:C0587248,OMIM:218040,ORPHA:3071,SNOMED CT:309776008; MedGen:C0949658, Orphanet:ORPHA155, Orphanet:ORPHA99739,SNOMED CT:83978005; MedGen:C1832243,OMIM:601494; MedGen:C1861864,OMIM:115195; MedGen:C2676271,OMIM:612422; MedGen:C3495498,OMIM:192600; MedGen:CN	1	201328373	201328373	NM_000364.3:c.853C>T	NP_000355.2:p.Arg285Cys	NC_000001.10:g.201328373G>A	OMIM Allelic Variant:191045.0004	C0587248 218040 Costello syndrome; C3495498 192600 Familial hypertrophic cardiomyopathy 1; C1861864 115195 Familial hypertrophic cardiomyopathy 2; C2676271 612422 Familial restrictive cardiomyopathy 3; C1832243 601494 Left ventricular noncompaction 6; C0