Patient Report |FINAL

Client: Example Client ABC123 Patient: Patient, Example 123 Test Drive Salt Lake City, UT 84108 DOB 12/31/1752 UNITED STATES Gender: Unknown Patient Identifiers: 01234567890ABCD, 012345 Physician: Doctor, Example Visit Number (FIN): 01234567890ABCD Collection Date: 01/01/2017 12:34

Hereditary - (SDHA) Sequencing ARUP test code 2011461 Hereditary PGL/PCC (SDHA) Seq - Spcmn Whole Blood

Hereditary PGL/PCC (SDHA) Seq - Interp Negative TEST PERFORMED - 2011461 TEST DESCRIPTION - Hereditary Paraganglioma-Pheochromocytoma (SDHA) Sequencing INDICATION FOR TEST - Confirm Diagnosis RESULT No pathogenic variants were detected in the SDHA . INTERPRETATION No pathogenic variants were detected in the SDHA gene by sequencing all coding regions and intron-exon boundaries. This result decreases the probability of, but does not exclude, a diagnosis of Hereditary Paraganglioma-Pheochromocytoma syndrome. Please refer to the background information included in this report for the clinical sensitivity and limitations of this test. RECOMMENDATIONS Medical screening and management should rely on clinical findings and family history. If there is suspicion for a hereditary cancer syndrome, consideration should be given to ordering the Hereditary Cancer Panel, Sequencing and Deletion/Duplication (ARUP test code 2012032). Genetic consultation is recommended. COMMENTS Reference Sequence: GenBank # NM_004168.2 (SDHA) Nucleotide numbering begins at the "A" of the ATG initiation codon. Likely benign and benign variants are not included in this report, but are available upon request.

This result has been reviewed and approved by

H=High, L=Low, *=Abnormal, C=Critical

Patient: Patient, Example ARUP Accession: 19-364-118902 Patient Identifiers: 01234567890ABCD, 012345 Visit Number (FIN): 01234567890ABCD Page 1 of 2 | Printed: 1/28/2021 2:43:30 PM 4848 Patient Report |FINAL

BACKGROUND INFORMATION: Hereditary Paraganglioma-Pheochromocytoma (SDHA)Sequencing CHARACTERISTICS: Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome is characterized by (neuroendocrine tumors of the autonomic nervous system) and (paragangliomas of the adrenal medulla). Pathogenic germline mutations in a number of , including SDHA, predispose to paraganglioma and pheochromocytoma with risk of malignant transformation. INCIDENCE: About 1 in 300,000 per year. INHERITANCE: Autosomal dominant. CAUSE: Pathogenic , subunits A, B, C, and D (SDHA, SDHB, SDHC, and SDHD) gene mutations. Mutations in other genes, including TMEM127, EGLN1, MAX, and SDHAF2, may also be causative. CLINICAL SENSITIVITY: Less than 3 percent. METHODOLOGY: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHA gene. Sequencing primers are specifically selected to target the functional SDHA gene. Analytical Sensitivity and Specificity: 96 percent. LIMITATIONS: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications in SDHA are not detected. In some cases, results may be uninterpretable due to technical limitations in the presence of . This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation. Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com. See Compliance Statement C: www.aruplab.com/CS

VERIFIED/REPORTED DATES

Procedure Accession Collected Received Verified/Reported

Hereditary PGL/PCC (SDHA) Seq - Spcmn 19-364-118902 12/30/2019 4:11:00 PM 12/30/2019 4:15:01 PM 1/9/2020 11:44:00 AM

Hereditary PGL/PCC (SDHA) Seq - Interp 19-364-118902 12/30/2019 4:11:00 PM 12/30/2019 4:15:01 PM 1/9/2020 11:44:00 AM

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H=High, L=Low, *=Abnormal, C=Critical

Patient: Patient, Example ARUP Accession: 19-364-118902 Patient Identifiers: 01234567890ABCD, 012345 Visit Number (FIN): 01234567890ABCD Page 2 of 2 | Printed: 1/28/2021 2:43:30 PM 4848