Patient Name: Birthdate (YYYY-MM-DD): 555 University Avenue Room 3416, Roy C. Hill Wing Gender:  Male  Female Toronto, ON, M5G 1X8, Canada Parent’s Name: Tel: 416-813-7200 x1 Address: Fax: 416-813-7732 (CLIA # 99D1014032) Telephone #: For Canada Only Genome Diagnostics Provincial Health Card #: Version: www.sickkids.ca/genome-diagnostics Issuing Province:

Referring Physician: Test request (write below and/ or check box(es) on pages 2 and 3):

Name:

Address: Reason for Testing:  Diagnosis  Carrier testing

Phone Fax  Familial mutation/variant analysis  Prenatal testing  Bank DNA only Email address:  Other (Specify):

Signature (required) If expedited testing is requested, please indicate reason  Pregnancy (Gestational age (weeks): ) Copy Report To:  Other (Specify: ) Name: Familial Mutation/Variant Analysis: Address: For prenatal testing and cases where a familial mutation or variant is known, please complete below and attach a copy of the proband’s report:

Gene:

Phone Fax Mutation/variant(s):

SickKids Laboratory number: Sample Information: Date obtained (YYYY-MM-DD): ______-______-______SickKids Pedigree number:

Your referring laboratory reference #: Name of proband:  Blood in EDTA (purple top tube): min. 4 mL (0.5-3 mL for newborns) Relationship to proband/fetus:  DNA: min.10 ug in low TE buffer (Source: )  Direct CVS: min. 10 mg direct villi Clinical Diagnostics and Family History:  Cultured villi: 1-2 confluent T25 flasks Please draw or attach a pedigree and provide any relevant information  Amniocytes: 1-2 confluent T25 flasks below, including clinical and family history details, as this is important for  Tissue (Source: ) accurate interpretation of results.  Other (Specify: )

Laboratory Use:

Date (YYYY-MM-DD ) | Time Received: ______- ______- ______| ______h

Lab #:

Specimen type, amt & # of tubes: Ethnicity:

Comments: Ordering Checklist: c Specimen tube labeled with at least two identifiers c Completed test requisition form (pages 1-5) Clinical information must be provided on pages 4 -5 for all Next-Generation Sequencing tests. Testing will not proceed until these are provided. Pedigree No. / Patient No. ______/ ______c Completed billing form (page 6, if applicable)

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 1 of 6 555 University Avenue Room 3416, Roy C. Hill Wing Patient Name: Toronto, ON, M5G 1X8, Canada

Tel: 416-813-7200 x1 Birthdate (YYYY-MM-DD): Fax: 416-813-7732

(CLIA # 99D1014032) Gender:  Male  Female Genome Diagnostics

LIST OF TESTS AVAILABLE BY DISEASE For prenatal testing and cases where a familial mutation/variant is known, please include information on page 1.

22q11 Deletion Syndrome Cancer Related Tests Continued  22q11 deletion/duplication analysis BRAF testing   Angelman Syndrome BRAF digital PCR for p.V600E (c.1799T>A)  Methylation and deletion/duplication analysis Charge Syndrome  UPD15 analysis (please submit parental samples)  CHD7 Sanger sequence analysis Arrhythmogenic Right Ventricular Cardiomyopathy  CHD7 deletion/duplication analysis  Sanger sequence analysis panel (5 genes): DSC2, DSG2, DSP, PKP2, TMEM43  SH3BP2 recurrent mutation analysis Ashkenazi Jewish Carrier Screening  SH3BP2 Sanger sequence analysis  Recurrent mutation analysis (7 diseases): Congenital Muscular Dystrophies Bloom syndrome, Canavan disease, Familial Dysautonomia,  Fanconi Anemia Group C, Mucolipidosis Type IV, Niemann-Pick Sanger sequence analysis panel (5 genes): disease, Tay-Sachs disease FCMD, FKRP, POMGnT1, POMT1, POMT2  Atypical Hemolytic Uremic Syndrome / Connective Tissue Disease Membranoproliferative Glomerulonephritis Clinical information must be provided on pages 4 and 5   Sanger sequence analysis panel (8 genes): Ehlers Danlos Syndrome NGS panel (18 genes)  APLN, C3, CD46, CFB, CFH, CFHR5, CFI, THBD Osteogenesis Imperfecta NGS panel (17 genes)  Osteopetrosis and Disorders of Increased Bone Density Autoinflammatory Disease  NGS panel (9 genes) Clinical information must be provided on pages 4 and 5  Bone Involvement NGS panel (43 genes)  Recurrent Fever Syndrome (RFS) NGS panel (17 genes)  Deletion/duplication analysis  Hemophagocytic Lymphohistiocytosis (HLH) NGS panel (14 genes) Craniosynostosis  Deletion/duplication analysis  Apert Syndrome (FGFR2 recurrent mutations analysis) Becker Muscular Dystrophy  Crouzon Syndrome (FGFR2, FGFR3 recurrent mutation analysis)  DMD Sanger sequence analysis  Pfeiffer Syndrome (FGFR1, FGFR2, FGFR3 recurrent mutation analysis)  DMD deletion/duplication analysis  Saethre-Chotzen Syndrome (TWIST sequence analysis and FGFR3 recurrent mutation analysis) Beckwith-Wiedemann Syndrome  Non-Syndromic Craniosynostosis (FGFR3 recurrent mutation analysis)  IC1 and IC2 methylation and 11p15 deletion/duplication analysis  FGFR2, FGFR3 and TWIST deletion/duplication analysis  UPD11 analysis (please submit parental samples)  CDKN1C Sanger sequence analysis Cystic Fibrosis  CFTR recurrent mutation analysis Bone Marrow Transplantation  CFTR Sanger sequence analysis  Post-transplant monitoring  CFTR deletion/duplication analysis

Branchio-Oto-Renal Syndrome Dopamine Beta-Hydroxylase Deficiency  EYA1 Sanger sequence analysis  DBH Sanger sequence analysis  EYA1 deletion/duplication analysis Duchenne Muscular Dystrophy Caffey Disease  DMD Sanger sequence analysis  COL1A1 recurrent mutation analysis  DMD deletion/duplication analysis  DMD mRNA analysis (please contact the laboratory before ordering) Cancer Related Tests Fabry Disease Li-Fraumeni Syndrome  GLA Sanger sequence analysis  p53 Sanger sequence analysis  GLA deletion/duplication analysis  p53 deletion/duplication analysis  GLA mRNA analysis (please contact the laboratory before ordering)

Rhabdoid Tumour Predisposition Syndrome Focal Segmental Glomerulosclerosis  SMARCB1 Sanger sequence analysis  Sanger sequence analysis panel (5 genes):  SMARCB1 deletion/duplication analysis ACTN4, CD2AP, NPHS1, NPHS2, TRPC6

ALK testing  Fragile X Syndrome  ALK Sanger sequence analysis (only possible on high quality DNA)  FMR1 trinucleotide repeat analysis  ALK digital PCR for p.F1245V (c.3733T>G), p.F1174L (c.3522C>A), p.R1275Q (c.3824G>A)

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 2 of 6 555 University Avenue Room 3416, Roy C. Hill Wing Patient Name: Toronto, ON, M5G 1X8, Canada

Tel: 416-813-7200 x1 Birthdate (YYYY-MM-DD): Fax: 416-813-7732

(CLIA # 99D1014032) Gender:  Male  Female Genome Diagnostics

LIST OF TESTS AVAILABLE BY DISEASE For prenatal testing and cases where a familial mutation/variant is known, please include information on page 1.

Fragile X E Syndrome   Maternal Cell Contamination Studies  FMR2 trinucleotide repeat analysis (please send maternal sample) (See testing requirements) type 1/Legius syndrome  Gaucher Disease Clinical information must be provided on pages 4 and 5  GBA recurrent mutation analysis  NF1 sequence analysis  NF1 deletion/duplication analysis Hearing Loss: Non-Syndromic, Autosomal Recessive  SPRED1 sequence analysis  GJB2 Sanger sequence analysis  SPRED1 deletion/duplication analysis  GJB6 deletion/duplication analysis Neuronal Ceroid Lipofuscinoses (Batten Disease) Hearing Loss: Non-Syndromic, X-Linked  CLN1, CLN2 and CLN3 recurrent mutation analysis  POU3F4 Sanger sequence analysis  Sanger sequence analysis panel (8 genes):  POU3F4 deletion/duplication analysis CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10

Hearing Loss: Aminoglycoside-induced, Mitochondrial and   MTRNR1, MTTS1 recurrent mutation analysis Clinical information must be provided on pages 4 and 5  Noonan Syndrome and RASopathies panel (13 genes) Hearing Loss: Pendred Syndrome  Deletion/duplication analysis for SPRED1 only  SLC26A4 Sanger sequence analysis  SLC26A4 deletion/duplication analysis Prader-Willi Syndrome Hereditary Hearing Loss   Methylation and deletion/duplication analysis Clinical information must be provided on pages 4 and 5  UPD15 analysis (please submit parental samples) When the Common and Non-syndromic Hearing Loss NGS Panel is requested, testing will begin with GJB2 and GJB6 testing. If negative, Russell-Silver Syndrome reflex testing to NGS testing will be initiated.  IC1 methylation and 11p15 deletion/duplication analysis  UPD7 analysis (please submit parental samples)  Common and Non-syndromic Hearing Loss NGS panel (56 genes)  Usher Syndrome NGS panel (9 genes) Shwachman-Diamond Syndrome  Stickler Syndrome NGS panel (6 genes)  SBDS Sanger sequence analysis (exon 2 only)  Alport Syndrome, Norrie Syndrome, Treacher Collins Syndrome, Waardenburg Syndrome NGS panel (9 genes) Simpson-Golabi-Behmel Syndrome  Deletion/duplication analysis  GPC3 Sanger sequence analysis Hereditary Hemorrhagic Telangiectasia  GPC3 and GPC4 deletion/duplication analysis  ACVRL1 Sanger sequence analysis Skeletal Dysplasia  ENG Sanger sequence analysis   ACVRL1 and ENG deletion/duplication analysis Achondroplasia (FGFR3 recurrent mutation analysis)   SMAD4 Sanger sequence analysis Hypochondroplasia (FGFR3 recurrent mutation analysis)  Thanatophoric Dysplasia (FGFR3 recurrent mutation analysis) Hereditary Spastic Paraplegia  Clinical information must be provided on pages 4 and 5 Spinal and Bulbar Muscular Atrophy  Autosomal Dominant HSP NGS panel (12 genes)  AR trinucleotide repeat analysis  Autosomal Recessive HSP NGS panel (36 genes)  X-Linked HSP NGS panel (3 genes) Spinal Muscular Atrophy  Deletion/duplication analysis  SMN1 and SMN2 deletion/duplication analysis

Hunter Disease Trismus Pseudocamptodactyly Syndrome  IDS Sanger sequence analysis  MYH8 Sanger sequence analysis  IDS deletion/duplication analysis  IDS mRNA analysis (please contact the laboratory)  X-Inactivation Analysis

Identity Testing  Other:  Tissue matching  Zygosity studies

 Next-Generation Sequencing (NGS) testing will only be initiated if the clinical  Testing for research/investigational purposes only information sections, located on pages 4 and 5 of the requisition form, are completed. For more information on our Next-Generation Sequencing (NGS)  For information on the testing requirement for Fragile X E, please visit the panels, including the list of genes tested, please visit our website: Specimen Requirements section for Fragile X E Syndrome on our website: www.sickkids.ca/genome-diagnostics www.sickkids.ca/genome-diagnostics/FragileXE

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 3 of 6 555 University Avenue Patient Name: Room 3416, Roy C. Hill Wing Toronto, ON, M5G 1X8, Canada Birthdate (YYYY-MM-DD):

Tel: 416-813-7200 x1   Fax: 416-813-7732 Gender: Male Female (CLIA # 99D1014032)

Genome Diagnostics Clincial Information (Required)

DISEASE SPECIFIC FEATURES Autoinflammatory Disorders Connective Tissue Disorders Hereditary Spastic Paraplegia Neurofibromatosis type 1 (NF1) / (RFS/HLH)  Ascending aortic dilation (HSP) Legius syndrome  Abnormal inflammatory response  Aortic dissection  Abnormal corpus callosum  The patient meets the NIH criteria  Fevers  Mitral valve regurgitation  Cognitive impairment for a clinical diagnosis of NF1  Arthritis  Mitral valve prolapse  Ataxia  Spasticity (≥2 of the clinical features below).  Pulmonary complications  Bicuspid aortic valve  Hyperreflexia  Seizures  ≥6 café-au-lait macules  Gastrointestinal irritation  Pulmonary hypertension  Extensor plantar reflex  , ≥ 2 or ≥ 1 Plexiform  Hepatosplenomegaly  Cleft palate  Other:  Freckling, axillary or inguinal  Lymphadenopathy  High arched palate The following investigations are  Optic  Hemophagocytosis  Micrognathia required before molecular testing of  ≥2 Lisch nodules (iris )  Oral ulcers  Retrognathia HSP is undertaken:  Osseous lesion (type: )  Rash, specify:  Bifid uvula   First degree relative diagnosed with   Loose/stretchable skin MRI – Brain and spinal cord Ocular inflammation specify: NF1 by above criteria  Edema (periorbital, optic disk)  Translucent skin  Biochemical testing - Vitamin B12,  Vision loss  Easy bruising vitamin E, very long chain fatty acids,  If the patient does not meet the NIH  Other:  Myopia lysosomal work-up, plasma amino criteria for a clinical diagnosis of  Lens dislocation acids and serum lipoprotein analysis NF1, rationale for testing must be Hearing Loss  Blue/gray sclerae (as appropriate) provided on page 5.  Age of onset:  Joint hypermobility   Joint pain Sensorineural hearing loss Noonan Syndrome and RASopathies   Scoliosis Conductive hearing loss  Increased nuchal translucency  Developmental delay  Arachnodactyly  Mixed hearing loss  Characteristic facies  Broad or webbed neck   Bilateral  Unilateral Club foot  Heart defect (specify: )  Hypertrophic cardiomyopathy  Syndromic  Non-syndromic  Thumb sign  Short stature (%ile: )  Pectus deformity  Ear anomalies  Ear tags  Wrist sign  Lymphatic dysplasias  Eye anomalies  Renal anomalies  Pectus deformity  Characteristic hematological abnormality (specify: )  White forelock  Cardiac anomalies  Other:  Other RASopathy features: (specify: )  Hirschsprung disease  For postnatal patients: The patient must present with ≥2 of the above  Other: features for molecular testing to be undertaken

GENERAL CLINICAL INFORMATION Perinatal history Craniofacial/Ophthalmalogic Gastrointestinal Neurological/Muscular  Premature birth  Abnormal face shape  Gastroschisis/omphalocele  Ataxia  Hypotonia  IUGR  Blindness  Cataracts  Gastrointestinal reflux  Chorea  Hypertonia  Oligohydramnios  Polyhydramnios  Coloboma  Optic atrophy  Pyloric stenosis  Dystonia  Spasticity  Other:  Opthalmoplegia  Ptosis  Tracheoesophageal fistula  Exercise intolerance/ easy fatigue  Retinitis pigmentosa  Hepatic failure  Headache/migraine Growth  Oral cleft  Chronic intestinal pseudo-obstruction  Muscle weakness  Failure to thrive  Other:  Hirschsprung disease  Seizures (type: )  Growth retardation/short stature  Recurrent vomiting  Stroke/stroke-like episodes  Overgrowth Brain malformations/  Chronic diarrhea  Other:   Microcephaly abnormal imaging  Constipation  Other:  Abnormality of the basal ganglia  Other: Skeletal/Limb abnormalities  Agenesis of the corpus callosum  Contractures  Club foot Physical/cognitive development  Brain atrophy Genitourinary abnormalities   Syndactyly  Delayed fine motor development  Cortical dysplasia  Ambiguous genitalia  Vertebral anomaly  Scoliosis  Delayed gross motor development  Hemimegalencephaly  Cryptorchidism  Other:  Delayed speech and language  Heterotopia  Hypospadias  Autistic behavior Skin/Hair  Holoprosencephaly  Hydronephrosis  Intellectual disability  Abnormality of the hair pattern,  Hydrocephalus  Kidney malformation  Developmental regression quantity  Lissencephaly  Renal agenesis  Other:  Abnormal nail growth  Periventricular leukomalacia  Proximal renal tubulopathy  Abnormal pigmentation  Other:  Other: Behavioral  Café-au-lait macules  Autistic features Cardiac/congenital heart Endocrine  Neoplasms of the skin  Obsessive-compulsive disorder  Diabetes mellitus Type 1  Neurofibromas  Other psychiatric symptoms malformations  ASD  VSD  Diabetes mellitus Type 2  Blistering  Other:  Coarctation of aorta  Hypothyroidism  Ichthyosis Cancer/Malignancy  Hypoplastic left heart  Hypoparathyroidism  Other:  Age of onset:  Tetralogy of Fallot  Pheochromocytoma/paraganglioma  Tumor type:  Cardiomyopathy  Other:  Location(s):  Arrhythmia/conduction defect  Other:

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 4 of 6 555 University Avenue Room 3416, Roy C. Hill Wing Patient Name: Toronto, ON, M5G 1X8, Canada

Tel: 416-813-7200 x1 Birthdate (YYYY-MM-DD): Fax: 416-813-7732

(CLIA # 99D1014032) Gender:  Male  Female Genome Diagnostics

Additional Relevant Clinical Information

Previous  No  Yes – Test Results

Ethnicity:

Family History

Please draw or attach a pedigree and provide any relevant information below, including clinical and family history details, as this is important for accurate interpretation of results.

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 5 of 6 Patient Name: 555 University Avenue Room 3416, Roy C. Hill Wing Birthdate (YYYY-MM-DD): Toronto, ON, M5G 1X8, Canada Gender:  Male  Female Tel: 416-813-7200 x1 Fax: 416-813-7732 (CLIA # 99D1014032) Completion of Billing Form NOT required for patients Genome Diagnostics with an Ontario Health Card Number.

BILLING FORM

At your direction, we will bill the hospital, referring laboratory, referring physician, or a patient/guardian, for the services we render • Invoices are sent upon completion of each test/service. • Invoices are itemized and include the date of service, patient name, CPT code, test name and charge. • Contact SickKids’ Genome Diagnostics Laboratory at 416-813-7200 x1 with billing inquiries.

How to complete the Billing Form: • Referring Physician completes the appropriate section below to specify billing method. • Send requisition and completed “Billing Form” with specimen.

Section 1: Complete to have the Healthcare Provider billed:

Your Referring Laboratory’s Reference #:

Billing address of hospital, referring laboratory, clinic, referring physician, or medical group: (if different from requisition): Name: Address: City: Prov/State: Postal/Zip Code: Country:

Contact Name: Contact Telephone #:

Section 2: Complete to have Patient/Guardian billed directly:

If you elect to have patient/guardian billed: • Patient/Guardian billing information below must be complete; otherwise, the healthcare provider will be billed. • Please advise the patient/guardian to expect a bill from our laboratory. • Provide us with patient’s valid credit card information. • Unfortunately, we cannot accept personal checks. • In this case, the patient/guardian is solely responsible for the charges.

Send bill to (check one):  Patient  Guardian

Method of Payment (check one):  American Express  MasterCard  Visa

Name as it appears on credit card:

Credit card # :

Expiry date on credit card:

Signature of credit card holder (Required):

Mailing Address of Patient/Guardian (if different from requisition): Additional Contact Information

Name: Patient’s phone # with area code: Address: Apt. #: - or - City: Prov/State: Guardian’s phone # with area code: Postal/Zip Code: Country:

DPLM Form #: OPL1000RGA-Ext/15, 2017-01-23 Referred-in Client Requisition Page 6 of 6