Patient Name: Date of Birth (DD/MM/YYYY): 555 University Avenue Room 3416, Roy C. Hill Wing Gender:  Male  Female MRN: Toronto, ON, M5G 1X8, Canada Parent’s Name: Tel: 416-813-7200 x1 Address: Fax: 416-813-7732 (CLIA # 99D1014032) Telephone #: For Canada Only (Billing section must be completed for all non-OHIP) 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:

Facility/Ward/Clinic (required): Reason for Testing: Address:  Diagnosis  Carrier testing  Familial mutation/variant analysis  Prenatal testing Phone Fax  Bank DNA only  Other (Specify): Email address: If expedited testing is requested, indicate reason Signature (required)  Pregnancy (Gestational age (weeks): )  Other (Specify: ) Copy Report To (if selected, all below information is required): Familial Mutation/Variant Analysis: Name: For prenatal testing and cases where a familial mutation or variant is known, Address: complete below and attach a copy of the proband’s report:

Gene & NM#:

Phone Fax Mutation/variant(s):

SickKids Laboratory/Order number:

Sample Information: SickKids Pedigree/Family number: Date obtained (DD/MM/YYYY): ______-______-______Name of proband: Referring laboratory reference #: Relationship to proband/fetus:  Blood in EDTA (purple top tube): min. 4 mL (0.5-3 mL for newborns) Name(s) & DOB of other submitted family members  DNA: min.10 ug in low TE buffer (Source: )  Direct CVS: min. 10 mg direct villi  Cultured villi: 1-2 confluent T25 flasks  Cultured amniocytes: 1-2 confluent T25 flasks  Tissue (Source: ) Ordering Checklist:  Other (Specify: ) c Specimen tube labeled with at least two identifiers Closed consent: c Completed test requisition form (pages 1-5)  (If checked, all remaining DNA will be discarded upon notification by the Clinical information must be provided on pages 4 -5 for all ordering physician that all DNA testing has been completed) Next-Generation Sequencing tests. Testing will not proceed until these are provided. c Completed billing form (page 6, if applicable) Laboratory Use:

Date (DD/MM/YYYY) | Time Received: Clinical Diagnostics and Family History: ______- ______- ______| ______h Draw or attach a pedigree and provide any relevant information below, including clinical and family history details, as this is important for accurate Lab #: interpretation of results

Specimen type, amt & # of tubes:

Comments:

______Pedigree No. / Patient No. ______/ ______Ethnicity:

DPLM Form #: OPL1000RGA-Ext/20, 2020/11/11 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 Date of Birth (DD/MM/YYYY): Fax: 416-813-7732

(CLIA # 99D1014032) Gender:  Male  Female MRN: 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 Charge Syndrome  22q11 deletion/duplication analysis  CHD7 sequence analysis  CHD7 deletion/duplication analysis Angelman Syndrome  Methylation and deletion/duplication analysis  UPD15 analysis (submit parental samples)  SH3BP2 recurrent mutation analysis  SH3BP2 sequence analysis Arrhythmogenic Right Ventricular Cardiomyopathy  Sequence analysis panel: Congenital Muscular Dystrophies DSC2, DSG2, DSP, PKP2, TMEM43  Sequence analysis panel: FKTN (FCMD), FKRP, POMGnT1, POMT1, POMT2 Ashkenazi Jewish Carrier Screening Use: Carrier Screening: Tay-Sachs Enzyme Testing & Connective Tissue Disease  Ashkenazi Jewish Molecular Panel Requisition Clinical information must be provided on pages 4 and 5 If more than one panel is requested, rationale must be provided on page 5. Atypical Hemolytic Uremic Syndrome /  Ehlers Danlos Syndrome NGS panel Membranoproliferative Glomerulonephritis  Osteogenesis Imperfecta NGS panel  Sequence analysis panel  Osteopetrosis and Disorders of Increased Bone Density NGS panel  Bone Involvement NGS panel  Deletion/duplication analysis Autoinflammatory Disease  Clinical information must be provided on pages 4 and 5 Craniosynostosis  Recurrent Fever Syndrome (RFS) NGS panel  Apert Syndrome (FGFR2 recurrent mutations analysis)  Hemophagocytic Lymphohistiocytosis (HLH) NGS panel  Crouzon Syndrome (FGFR2, FGFR3 recurrent mutation analysis)  Deletion/duplication analysis  Pfeiffer Syndrome (FGFR1, FGFR2, FGFR3 recurrent mutation analysis)  Saethre-Chotzen Syndrome (TWIST1 sequence analysis and FGFR3 Becker Muscular Dystrophy recurrent mutation analysis)  DMD Sequence analysis  Non-Syndromic Craniosynostosis (FGFR3 recurrent mutation analysis)  DMD deletion/duplication analysis  TWIST1 deletion/duplication analysis Beckwith-Wiedemann Syndrome Cystic Fibrosis  IC1 and IC2 methylation and 11p15 deletion/duplication analysis For prenatal echogenic bowel, ensure parental samples are linked to each  UPD11 analysis other on both requisitions with at least two identifiers. Ensure “echogenic  CDKN1C Sequence analysis bowel” is indicated on the Family History section on Page 1.  Bone Marrow Transplantation CFTR recurrent mutation analysis  CFTR Sequence analysis  Post-transplant monitoring  CFTR deletion/duplication analysis Branchio-Oto-Renal Syndrome Dopamine Beta-Hydroxylase Deficiency  EYA1 Sequence analysis  DBH Sequence analysis  EYA1 deletion/duplication analysis Duchenne Muscular Dystrophy Caffey Disease  DMD Sequence analysis  COL1A1 recurrent mutation analysis  DMD deletion/duplication analysis  DMD mRNA analysis (contact the laboratory before ordering) Cancer Related Tests Li-Fraumeni Syndrome Fabry Disease  TP53 Sequence analysis  GLA Sequence analysis  TP53 deletion/duplication analysis  GLA deletion/duplication analysis  GLA mRNA analysis (contact the laboratory before ordering) Rhabdoid Tumour Predisposition Syndrome Focal Segmental Glomerulosclerosis  SMARCB1 Sequence analysis   SMARCB1 deletion/duplication analysis Sequence analysis panel

Fragile X Syndrome  FMR1 trinucleotide repeat analysis

DPLM Form #: OPL1000RGA-Ext/20, 2020/11/11 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 Date of Birth (DD/MM/YYYY): Fax: 416-813-7732

(CLIA # 99D1014032) Gender:  Male  Female MRN: 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  AFF2 trinucleotide repeat analysis (maternal sample required) (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 Sequence analysis  SPRED1 deletion/duplication analysis  GJB6 deletion/duplication analysis Neuronal Ceroid Lipofuscinoses (Batten Disease) Hearing Loss: Pendred Syndrome  PPT1 (CLN1), TPP1 (CLN2) and CLN3 recurrent mutation analysis  SLC26A4 Sequence analysis  Sequence analysis panel:  SLC26A4 deletion/duplication analysis PPT1(CLN1), TPP1 (CLN2), CLN3, CLN5, CLN6, CLN7, CLN8, CLN10  Hereditary Hearing Loss and  Clinical information must be provided on pages 4 and 5 Clinical information must be provided on pages 4 and 5 When the Common and Non-syndromic Hearing Loss Panel is requested,  Noonan Syndrome and RASopathies panel STRC dosage is tested.  Deletion/duplication analysis for SPRED1 only  Common and Non-syndromic Hearing Loss NGS panel  Usher Syndrome NGS panel Prader-Willi Syndrome  Stickler Syndrome NGS panel  Methylation and deletion/duplication analysis  Alport Syndrome, Norrie Syndrome, Treacher Collins Syndrome,  UPD15 analysis (parental samples required) Waardenburg Syndrome NGS panel  Deletion/duplication analysis Russell-Silver Syndrome  IC1 methylation and 11p15 deletion/duplication analysis Hereditary Hemorrhagic Telangiectasia  UPD7 analysis (parental samples required)  ACVRL1 Sequence analysis  ENG Sequence analysis Shwachman-Diamond Syndrome  ACVRL1 and ENG deletion/duplication analysis  SBDS Sequence analysis  SMAD4 Sequence analysis Simpson-Golabi-Behmel Syndrome Hereditary Spastic Paraplegia   Clinical information must be provided on pages 4 and 5 GPC3 sequence analysis and GPC3 and GPC4 deletion/duplication analysis  Autosomal Dominant HSP NGS panel  Autosomal Recessive HSP NGS panel Skeletal Dysplasia  X-Linked HSP NGS panel   Deletion/duplication analysis Achondroplasia (FGFR3 recurrent mutation analysis)  Hypochondroplasia (FGFR3 recurrent mutation analysis) Hunter Disease  Thanatophoric Dysplasia (FGFR3 recurrent mutation analysis)  IDS Sequence analysis  IDS deletion/duplication analysis Spinal and Bulbar Muscular Atrophy  IDS mRNA analysis (contact the laboratory before ordering)  AR trinucleotide repeat analysis

Identity Testing Spinal Muscular Atrophy  Zygosity studies  SMN1 and SMN2 deletion/duplication analysis

Trismus Pseudocamptodactyly Syndrome  MYH8 Sequence analysis

 X-Inactivation Analysis

 Other:

 Next-Generation Sequencing (NGS) testing will only be initiated if the clinical 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/20, 2020/11/11 Referred-in Client Requisition Page 3 of 6 555 University Avenue Patient Name: Room 3416, Roy C. Hill Wing Toronto, ON, M5G 1X8, Canada Date of Birth (DD/MM/YYYY):

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

Genome Diagnostics Clinical Information (Required)

DISEASE SPECIFIC FEATURES Autoinflammatory Disorders Hearing Loss Hereditary Spastic Paraplegia (HSP) Neurofibromatosis type 1 (NF1) / (RFS/HLH)  Age of onset:  Abnormal corpus callosum Legius Syndrome  Abnormal inflammatory response  Sensorineural hearing loss  Cognitive impairment  The patient meets the NIH criteria  Fevers  Conductive hearing loss  Ataxia  Spasticity for a clinical diagnosis of NF1  Arthritis  Mixed hearing loss  Hyperreflexia  Seizures (>2 of the clinical features below).  Pulmonary complications  Bilateral  Unilateral  Hypertonia  Hypotonia  Café-au-lait macules  Gastrointestinal irritation  Syndromic  Non-syndromic  Dystonia  Dysarthria  ≥6 CALS  (#: )  Hepatosplenomegaly  Ear anomalies  Ear tags  Extensor plantar reflex  , ≥ 2 or ≥ 1 Plexiform  Lymphadenopathy  Eye anomalies  Renal  Other:  Freckling, axillary or inguinal  Hemophagocytosis anomalies  Optic The following investigations are  Oral ulcers  White forelock  Cardiac  ≥2 Lisch nodules (iris ) required before molecular testing  Rash, specify: anomalies  Osseous lesion (type: ) of HSP is undertaken:  Ocular inflammation specify:  Hirschsprung disease  First degree relative diagnosed with  Edema (periorbital, optic disk)  Other:  MRI – Brain and spinal cord NF1 by above criteria  Vision loss  Other:  Biochemical testing - Vitamin B12,  Other:  vitamin E, very long chain fatty acids, The patient does not meet the NIH lysosomal work-up, plasma amino diagnostic criteria for NF1. acids and serum lipoprotein analysis Rationale for testing must be (as appropriate) provided on page 5. Connective Tissue Disorders (CTD) Noonan Syndrome and RASopathies Ehlers Danlos Syndrome (EDS) Osteogenesis Imperfecta (OI)  Increased nuchal translucency  Indicate the suspected clinical diagnosis If the patient does not present with one of the test indications below, rationale Developmental delay  in the patient: for testing must be provided on page 5. Characteristic facies   Classic  Vascular  Fetal findings on anatomy ultrasound consistent with OI. Broad or webbed neck   Kyphoscoliotic  Other:  Fractures with minimal or no trauma in the absence of other Heart defect (specify: )  Note: is not offered for known disorders of bone metabolism. Hypertrophic cardiomyopathy  joint hypermobility alone. If testing is  Vertebral fractures Short stature (%ile: )  requested for joint hypermobility, provide  Dentinogenesis imperfecta Pectus deformity  rationale on page 5.  Low ALP for age/gender (ALPL analysis only will be performed) Lymphatic dysplasias  Characteristic hematological Check applicable CTD features below. Check applicable CTD features below. abnormality (specify: ) Osteopetrosis and Disorders of Bone Involvement  Other RASopathy features: Increased Bone Density Check applicable CTD features below. (specify: ) Check applicable CTD features below.  For postnatal patients: The patient CTD Related Clinical Features: must present with ≥2 of the above  Joint hypermobility:  Easy bruising  Recurrent pneumothoraces features for molecular testing to Beighton score:  Myopia  Joint subluxations/dislocations be undertaken.  Arterial aneurysms, dissection or  Lens dislocation  Fractures rupture  Blue/gray sclerae  Bone deformity  Intestinal rupture  Thumb or wrist sign  Wormian bones  Molluscoid pseudotumors  Club foot  Increased bone mineral density  Subcutaneous spheroids  Scoliosis  Diaphyseal sclerosis  Loose/stretchable skin  Marfanoid habitus  Hearing loss  Smooth/velvety skin  Short stature  Osteosclerosis  Widened atrophic scars  Shortened long bones  Other:  Recurrent spontaneous tendon rupture

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.

Ethnicity: DPLM Form #: OPL1000RGA-Ext/20, 2020/11/11 Referred-in Client Requisition Page 4 of 6 555 University Avenue Patient Name: Room 3416, Roy C. Hill Wing Toronto, ON, M5G 1X8, Canada Date of Birth (DD/MM/YYYY):

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

Genome Diagnostics Clinical Information (Required)

ADDITIONAL RELEVANT CLINICAL INFORMATION Previous Genetic Testing  No  Yes – Test Results

GENERAL CLINICAL FEATURES 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/20, 2020/11/11 Referred-in Client Requisition Page 5 of 6 Patient Name: 555 University Avenue Room 3416, Roy C. Hill Wing Date of Birth (DD/MM/YYYY): Toronto, ON, M5G 1X8, Canada Gender:  Male  Female MRN: 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

The hospital, referring laboratory, or a patient/guardian will be billed for the services rendered. • Invoices are sent upon completion of each test/service. • 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.

Option 1: Complete to have the Healthcare Provider billed: Option 2: Interm Federal Health Program (IFHP)

Your Referring Laboratory’s Reference #: ______Submit a copy of the Interim Federal Health Certificate (Refugee

Billing address of hospital, referring laboratory: Protection Claimant Document) with the photo and UCI# visible for Name: coverage to be confirmed. Address: UCI# City: Prov/State: Postal/Zip Code: Country: ICD code (lab use only):

Contact Name: Contact Telephone #:

Option 3: 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.

Relation to patient (check one):  Patient  Guardian/Parent

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

Name as it appears on credit card:

Credit card # :

Expiry date on credit card:

CVS#- found on back of card (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/20, 2020/11/11 Referred-in Client Requisition Page 6 of 6