Whole Exome Sequencing - CentoXome® - CENTOGENE

Whole Exome Sequencing - CentoXome ®› Test RequestedCentoXome® basic (raw data)CentoXome® extended (bioinformatic analysis of the raw data)CentoXome® advanced (bioinformatic analysis and validationof the sequencing results by Sanger sequencing , includingan extended clinical report )Will you send additional familial samples?Yes NoIf relatives‘ samples will be sent, please list all relatives(please add an informative pedigree):1. ›2. ›3. ›Name First name Date of birthRelationship to patientAffected: Yes NoName First name Date of birthRelationship to patientAffected: Yes NoName First name Date of birthRelationship to patientAffected: Yes No› Patient InformationLast NameFirst NameDate of Birth (day/month/year)Sex Male FemaleStreetZIP Code/TownCountryYour Reference NumberSample Collection Date› Additional Report RecipientName of PhysicianClinicDepartmentStreetZIP Code/TownCountryPhoneFax › Physician or Laboratory (Reporting Address)Name of PhysicianE-MailClinicDepartmentStreetZIP Code/TownCountryPhoneE-MailFax › BillingCENTOGENE Quotation Nr.Invoice to Patient Clinic/InsurancePlease attach Authorization/ReferralNameDepartmentStreetZIP Code/Town› Minimum Sample RequirementsEDTA Blood (≈ 1 ml)High Quality Prepared DNA (≈ 1 μg)CountryPhoneE-MailFax WES_V1_November 20131 of 4 pagesISO/EN 15189CLIA #99D2049715

› Declaration of Accordance with Legal RegulationsBy signing this consent form, I certify that this requestis placed in accordance with the legal regulations in ourcountry related to genetic testing.Place, DateSignature of PhysicianMandatory› Declaration of Consent for the Performanceof a Genetic AnalysisI consent to the carrying out of the genetic investigation(s) indicatedon these pages, on myself or the person I am custodian for.I agree to the recording of my personal data, especially my name,date of birth and relationship to other family members and ofrequired medical data, in accordance with data protec tion regulations.I further agree that the result(s) of the investigation may berecorded for purposes of their transmittance to me or my attendingphysician in accordance with data protection regulations.The recorded data will not be forwarded to anybody un authorized.I have been comprehensively informed by my physicianof the medical and psychological consequences. I also confirmthat I will receive genetic counseling to help me understandthe impact and consequences of my diagnostic results.Furthermore I have been informed about the significanceand consequences of the planned investigations. I have beeninformed that, especially in the case of familial genetic investigations,correct information about the relationships betweenfamily members is of importance.Should I have further questions I can contact my attendingphysician or a medical consultant of the analytical laboratory.Place, DateSignature of Patient/GuardianMandatory› Coverage by Healthcare System/Clinic/InsurancePlace, DateYes NoSignature of PhysicianSignature of Patient/Guardian› Alternative: in Case of Direct Billing to the PatientPlace, DateI authorize the physician to request this analysis/these analysesand I am informed about the costs. I herewith undertake tobe liable for the payment of any invoice related to this diagnosticsand I declare that the address given above is the correctbilling address.Signature of Patient/GuardianWES_V1_November 20132 of 4 pages

Consent Form Whole Exome SequencingExome sequencing has the potential to detect diseases whichthe patient may wish to be informed about. Typically thesediseases can be categorized as:1) a predisposition to increased cancer risk;2) carrier status of recessive diseases;3) a predisposition to late-onset diseases.We need the signature of the physician to confirm that thepatient has been informed of the above information. Thepatient´s signature confirms whether he/she chooses to beinformed about the results of 1) to 3).Place, DatePhysician‘s printed namePatient‘s printed nameSignature of PhysicianSignature of Patient/GuardianMandatoryIn addition to the most modern technology and continuoustraining, Centogene´s analytical and research work forms thebasis for constant further development. Therefore, Centogenerequests your permission to use any excess samples for futureresearch and development, while guaranteeing that such sampleswill always be fully anonymous.If an exome test is cancelled prior to test set-up, Centogenecharges a processing fee and will send a cancellation report.Once testing is initiated, the full price of the analysis will becharged.I consent to the use of my DNA sample for research anddevelopment purposes.Yes Place, DateNoSignature of Patient/GuardianI understand and accept my financial responsibilities.Place, DateMandatorySignature of Patient/GuardianAs our whole exome sequencing test is analyzing many differentgenes, there is a potential for the recognition of incidentalor secondary findings unrelated to the reason for ordering WES.These findings can provide information that was not anticipatedand that are unrelated to the individual’s reported clinicalfeatures, but are of medical value for patient care.I choose to receive information regarding genetic results thatare unrelated to the specific reason for which my health careprovider ordered the test.Yes NoCentogene reports mutations of the specified classes ortypes in the genes listed in the „ACMG Recommendations forReporting of Incidental Findings“ in clinical exome sequencingreport.Place, DateSignature of Patient/GuardianWES_V1_November 20133 of 4 pages

Clinical information is essential for accurate interpretation of whole exome results. Please check carefully all theitems that describe best the clinical phenotype of your patient or family members.Please tick the appropriate phenotype✘Please tick the appropriate phenotype✘Please tick the appropriate phenotype✘1. Metabolic disordersOphthalmoplegia8. LiverCardiomyopathyCarnitine reducedCK abnormalitiesCSF lactate increaseElevated alanineElevated pyruvateHepatosplenomegalyKetosisLactic acidemiaOrganic aciduria2. Neurological disordersAtaxiaAutismBrain atrophyChoreaCorpus callosum agenesisCortical dysplasiaDystoniaOptic atrophyPtosisRetinitisRetinoblastoma4. Ear, nose and throat disordersDeafnessEar malformationFailure to thrive5. Bone, Skin and immune disordersAbnormal hairAbnormal nailsAbnormal pigmentationAnemiaClub footContracturesGrowth retardationIchthyosisImmune deficiencyKidney and endocrine disordersConstipationDiabetes mellitusDiarrheaElevated transaminasesHepatic failureHepatosplenomegalyHirschsprung diseaseHypoparathyroidismHypothyroidismKidney malformationParagangliomaPheochromocytomaPyloric stenosisRecurrent vomitingRenal agenesisRenal tubulopathySplenomegaly9. Reproductive disordersHeadachePancytopeniaHypospadiasHeterotopiaPolydactylyInfertilityHoloprosencephalyHydrocephalusLeukodystrophyLissencephalyMacrocephalyMental retardationMicrocephalyMigraineMitochrondriopathyMuscle weaknessParkinsonPsychiatric syndromeSpasticityStroke3. Ophthalmological disordersBlepharospasmCataractColobomScoliosisSkin tumorsSyndactylyVertebral anomaly6. Cardiological disordersArrhythmiaCardiomyopathyCoarctation of aortaLong QT syndromeSeptum defectTetralogy of fallot7. Vascular disordersAngioedemaCoagulation disorderHypertensionHypotensionInfarctionStroke10. Tumoral and haematological disordersAdenomatous polyposisAnemiaBrain tumorBreast cancerColorectal tumorImmunodeficiencyLung tumorMelanomaNeurofibromatosisNeutropeniaPancytopeniaSickle cell anemia11. Malformation and retardation syndromesAgenesis of corpus callosumBrain atrophyCortical dysplasiaDementiaHemimegalencephalyGlaucomaVasculitis/angiitisHydrocepha› Contact Details Customer ServiceChief Medical DirectorWES_V1_November 20134 of 4 pagesPhone: +49 (0)381 203 652- 222Fax: +49 (0)381 203 652-19testing@centogene.comwww.centogene.comProf. Arndt Rolfs, MDPhone: +49 (0)381 203 652- 211arndt.rolfs@centogene.comPlease send your sample and therequisition form to:Centogene AGSchillingallee 6818057 Rostock, Germany