1274 Genetic Carrier Screening Panel (3 genes) includes: • Cystic Fibrosis Core Test (23 major CFTR variants approved by ACOG/ACMG) • Fragile X Syndrome • Spinal Muscular Atrophy

1247 Genetic Carrier Screening Ashkenazi Panel (43 genes) includes:

• Abetalipoproteinemia (MTTP) • Alport Syndrome (COL4A3) • Arthrogryposis, Mental Retardation, and Seizures• Bardet-Biedl Syndrome Bloom Syndrome • Canavan Disease • Carnitine Palmitoyltransferase II Deficiency • Congenital Amegakaryocytic Thrombocytopenia • Congenital Disorder of Glycosylation Type 1a • Cystic Fibrosis Comprehensive Test (191 variants)• Dyskeratosis Congenita • Ehlers-Danlos Syndrome Type VIIC • Familial Dysautonomia • Familial Hyperinsulinism • Fanconi Anemia Type C • Fragile X Syndrome • Galactosemia • Gaucher Disease • Glycogen Storage Disease 1a

1. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol 2017 Mar;129(3):e41-e55.

Genetic Carrier ScreeningAvailable from a blood, mouthwash, OneSwab® or ThinPrep®

ACOG Recommends Offering Carrier Screening to All Women,

Regardless of Ethnicity or Family History…

Now Available

• Joubert Syndrome • Maple Syrup Urine Disease Types 1a, 1b, 3 • Mucolipidosis Type IV • Multiple Sulfatase Deficiency • Nemaline Myopathy • Niemann-Pick Disease • Phosphoglycerate Dehydrogenase Deficiency • Polycystic Kidney Disease, Autosomal Recessive • Retinitis Pigmentosa 59 • Smith-Lemli-Opitz Syndrome • Spinal Muscular Atrophy • Tay-Sachs Disease • Tyrosinemia Type 1 • Usher Syndrome Type 1F and III • Walker-Warburg

Syndrome • Wilson Disease • Zellweger Spectrum Disorder

Medical Diagnostic Laboratories, L.L.C.www.mdlab.com • 877.269.0090

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Methods and Variant Classification:

Genomic DNA is extracted from blood or mouth wash sample. High-throughput next generation sequencing is performed to examine for the over 1,300 DNA variants which are associated with 41 diseases. Some mutations are more severe than others. These variant regions are sequenced to high coverage and the sequences are compared to standards and references of normal variation. All reported variants are confirmed by the “gold standard” Sanger sequencing. In addition, some of the variants on the panel may be partially subjected to Sanger sequencing due to inadequate sequence coverage by next generation sequencing. The MDL variant classification system is based on the 5-tier system recommendations for the interpretation of sequence variants proposed by the American College of Medical Genetics and Genomics (ACMG) and complies with the standards and guidelines for the interpretation of sequence variants by ACMG and the Association for Molecular Pathology (AMP) (Reference 1). To classify each variant, MDL assigns weight to each piece of available evidence, including literature reviews, reputable database reports, population frequencies, and computational In Silico analysis using PROVEAN, SIFT and MutationTaster and prediction. Any detected variants that are a recognized cause of the disease (Pathogenic) will be reported. In addition, variants that have not previously been established as a recognized cause of disease may be identified. In these cases, variants classified as "likely" pathogenic are reported too. Benign variants, likely benign variants and variants of uncertain significance, and variants not directly associated with the intended disease phenotype are not reported. MDL variant results are reported using numbering and nomenclature recommended by the Human Genome Variation Society (HGVS http://hgvs.org). All results are reported in reference to Human Genome 19, Human Build 37.

Residual Risk: � Residual risk is the possibility of being a carrier in the case of a negative test result for any genetic disease tested. A negative result for any of the diseases tested in the MDL carrier screening panel significantly decreases a person's risk of being a carrier for this genetic condition. However, it is still possible to be a carrier for a disease-associated variant that is not tested utilizing this panel. If there is a family history or concern about carrier status for a particular genetic condition and you would like to find out more, please contact your health provider or a genetic counselor. Included in the table below (Table 1) is the residual risk estimates for the carrier conditions in the MDL carrier screening test. Population pre-test carrier rate, carrier detection rate and residual risk are shown for conditions and specific populations for which the data is known. For other conditions listed below and populations that are not shown, the prevalence is rare, the mutation detection rate is unknown and residual risk is not calculable.

The classification and interpretation of all genetic variants identified as a result of this genetic testing is based on the current scientific information available. As new scientific information becomes available, in some circumstances, the classification and interpretation of the genetic variants may change.All test results should be interpreted by a physician or genetic counselor in the context of the personal/family history, and clinical and laboratory data. A “Positive” test result indicates the person is at higher risk for having a child with a genetic condition. Partner testing should be considered. Genetic counseling is recommended to review results, discuss additional testing possibilities, and evaluate any next steps. The patient was NEGATIVE for the variants tested for all other diseases. These results reduce, but do not eliminate, the chance to be a carrier. See carrier screening residual risk table for disease-specific details.

References/Footnotes:1. Sue Richards et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Genetics in Medicine 2015 May;17(5):405-24.

Disclaimer:This test was developed and its performance characteristics have been determined by Medical Diagnostic Laboratories, LLC. Performance characteristics refer to the analytical performance of the test. It is not been reviewed by the US Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary.

Test Limitations: � The MDL carrier screen panel analyses over 1,300 known targeted variants associated with 41 genetic diseases. Mutations are previously reported as the cause of the genetic diseases and selected for relatively high frequency in the general population or in specific ethnic populations. Therefore, the test detection rate varies for each disease and for each ethnic group. Interpretations and risk calculations are based on the ethnic information and clinical and family relationships provided, as well as the current understanding of the molecular genetics of the conditions tested. This test does not rule out the presence of disease-causing variants in other regions of the gene analyzed or potentially examine all genes associated with the disease, and will not detect germline mosaicism. Because of this, the MDL test is risk-reducing and not risk-eliminating. Residual risks reflect the remaining possibility that a patient is a carrier for additional variants not screened for in this test and are dependent on gender, ethnicity, and corresponding detection rates. People with certain histories or ethnicities may experience better carrier detection with other testing methods, and it is recommended that these options be reviewed with patients by their healthcare provider. In an unknown number of cases, nearby genetic variants may interfere with mutation detection. Other possible sources of diagnostic error include sample mix-up, trace contamination, bone marrow transplantation, blood transfusions and technical errors. If more than one variant is detected in a gene, additional studies may be necessary to determine if those variants exist on the same chromosome or on different chromosomes.

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MEDICAL DIAGNOSTIC LABORATORIES, L.L.C.

SSN: DOB:

MDL#: Test Results

Home #:

NPI:

202 Any StreetSpecimen Type:Date Collection:Date Received: Tel:Date Resulted: Fax:

Test Performed Inheritance

BLM Sequencing

Autosomal Recessive

ASPA Sequencing

CFTR Sequencing

IKBKAP Sequencing

FANCC Sequencing

GBA Sequencing

MCOLN1 Sequencing

SMPD1 Sequencing

HEXA Sequencing

Patient Information: 123-45-6789 12/12/1973 (Age: 43)

1234567 Doe, JaneGenetic Counselor Information:

www.mdlab.com TL: 609-570-1000. FX: 609-570-1050. TF: 877-269-0090

2439 KUSER ROAD. HAMILTON, NJ 08690-3303

Final

Genetic Carrier Screening Society-Guided Panel (9 genes)

Anytown, NJ 00000

555-555-5553

John Doe, MD.Doe Clinic

90 Trenton RoadAnytown, NJ 00000

555-555-5551 Patient ID: 123456

Mouthwash

Interpretation Summary:

Positive for Bloom Syndrome carrier. For partner, carrier testing should be considered.ClassificationVariant Zygosity Location Disease Parental Origin ReferenceGene Transcript

Variant Detected

No Variants Detected

Bloom Syndrome

Unknown

No Variants Detected

No Variants Detected

No Variants Detected

No Variants Detected

No Variants Detected

Comprehensive Interpretation:Test Interpretation: Sequencing of the known disease-associated mutations of 41 rare genetic disease-related genes was completed. The patient was POSITIVE for the variant c.2207_2212delATCTGAinsTAGATTC (p.Tyr736Leufs) in the BLM gene. This change has been associated with Bloom Syndrome and is considered to be the cause of the disorder. This variant was identified by Next Generation Sequencing (NGS) and classified using the MDL variant classification system (see below for detail). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 736 and leads to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein.

c.2207_2212delATCTGAinsTA

GATTC (p.Tyr736Leufs)

NM_000057.3

555-555-5554

1/5/20171/6/20171/16/2017

Ordering Physician/Lab:

No Variants Detected

No Variants Detected

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