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C-55 (Comprehensive Panel) Pathogenic Variant Detected

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C-55 (Comprehensive Panel) Pathogenic Variant Detected Capstone Healthcare 8601 Dunwoody Place, Building 400, Suite 444 Atlanta, GA 30350 www.capstonehealthcare.com 844-497-8851 Laboratory Director: John Hanson, PhD CLIA ID Number: 11D2073885 PATIENT INFORMATION PROVIDER INFORMATION SPECIMEN Patient Name: Sarah Doe Physician: Dr Jospeh Smith Accession ID: 10000520 Date of Birth: Apr 10, 1985 Client: St Michael Hospital Specimen Type: Buccal Swab Age: 33 Client ID: 123654 Collection Date: Aug 21, 2018 Sex: Female Date Accessioned: Aug 22, 2018 Ethnicity: Caucasian Date Reported: Sep 7, 2018 TEST PERFORMED C-55 (Comprehensive Panel) Targeted next-generation sequencing was performed on this specimen. See Methods and Limitations section for more information. RESULT Pathogenic Variant Detected An abnormality is detected that has been reported to be associated with an increased risk for hereditary cancer. This finding may help you and your doctor make more informed choices about your health care and develop a strategy for cancer prevention and monitoring. VARIANT SUMMARY Variants Detected Genotype Phenotype Assessment BRCA1 Susceptibility To Familial c.798_799delTT Heterozygous Breast-ovarian Cancer Pathogenic p.S267fs*19 Type 1 VARIANT INTERPRETATION BRCA1 Interpretation: BRCA1 is a tumor suppressor responsible for repair of DNA double strand c.798_799delTT breaks and maintenance of genomic stability [3]. Deletions, loss of heterozygosity, and loss-of- function mutations cause BRCA1 inactivation [7, 6]. p.S267fs*19 Pathogenic Capstone Healthcare | 8601 Dunwood Place | Building 400 | Suite 444 | Atlanta, GA | 30350 Page 1 of 3 Accession ID: 10000520 Laboratory Director: John Hanson, PhD CLIA ID Number: 11D2073885 C-55 (Comprehensive Panel) GENES TESTED APC, ATM, AXIN1, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDC73, CDH1, CDKN1C, CDKN2A, CHEK2, DICER1, DIS3L2, EPCAM, FH, FLCN, GPC3, GREM1, MEN1, MET, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PAKAR1A, PALB2, PMS2, POLD1, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, REQL4, RET, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARC4A, STK11, SUFU, TP53, TSC1, TSC2, VHL, WT1 METHODS AND LIMITATIONS DNA extracted from patient’s saliva sample is quantified using Qubit 2.0 Fluorimeter (Life Technologies Inc.). Germline mutations of APC, ATM, AXIN1, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDC73, CDH1, CDKN1C, CDKN2A, CHEK2, DICER1, DIS3L2, EPCAM, FH, FLCN, GPC3, GREM1, MEN1, MET, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PAKAR1A, PALB2, PMS2, POLD1, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RB1, REQL4, RET, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARC4A, STK11, SUFU, TP53, TSC1, TSC2, VHL, WT1 genes are tested by sequencing the entire coding region for each gene with 5 bp of padding at both ends. The panel consists of amplicons that cover 98% of all coding regions of the genes listed above. Each sample template is tagged with a unique barcode for sample identification before processing. Sequencing is performed on the Ion Torrent S5 (Life Technologies Inc.) using AmpliSeq and Ion Chef technologies, and Hi-Q View chemistry. Data obtained are analyzed using the Applied Biosystems Ion Torrent variant analyzing software, which includes signal processing, base calling,quality score assignment, adapter trimming, alignment to human genome 19 reference (hg19), coverage analysis, and variant calling. Variant annotation is performed on the QIAGEN Clinical Insight software. Sanger sequencing confirmation is performed on all pathogenic, likely pathogenic, and variant of unknown significance samples through Eurofins Clinical Molecular Testing Services, LLC. Based on validation studies, our method has a >95% sensitivity and specificity for detecting single nucleotide variants, insertions/deletions, and other frame shift mutations. However, some rare and novel genetic variations might not be detected by this method. Genes other then those listed above that are associated with certain types of cancer are beyond the scope of this test. QIAGEN Clinical Insight (QCITM) is a variant analysis, interpretation and decision support tool for research and clinical labs analyzing human genetics data and is not intended to be used for diagnostic purposes. QCI Interpret software includes the following underlying databases, data reference sets and tools; QIAGEN Clinical Insight-Interpret (5.3.20180727), Ingenuity Knowledge Base (Rohan 180831.001), CADD (v1.3), Allele Frequency Community (2018-05-25), EVS (ESP6500SI-V2), JASPAR (2013-11), Ingenuity Knowledge Base Snapshot Timestamp (2018-08-31 11:07:19.0), Vista Enhancer hg18 (2012- 07), Vista Enhancer hg19 (2012-07), Clinical Trials (Rohan 180831.001), PolyPhen-2 (v2.2.2), 1000 Genome Frequency (phase3v5b), ExAC (0.3.1), iva (Jun 26 11:55 iva-1.0.476233.jar), PhyloP hg18 (2009-11), PhyloP hg19 (2009-11), DbSNP (151), TargetScan (6.2), CentoMD (4.2), OMIM (May 26, 2017), gnomAD (2.0.1), BSIFT (2016-02-23), TCGA (2013-09-05), Clinvar (2018-04-06), DGV (2016-05-15), COSMIC (v84), HGMD (2018.1), SIFT4G (2016-02-23) DISCLAIMER False positives and false negatives are possible. Such errors can be due to contamination, technical errors, and interference from rare genetic variants. It is recommended to consider alternative methods before taking any clinical action. Consulting your results with a genetic counselor is highly recommended. This test was developed, and its performance characteristics determined by Capstone Healthcare. The laboratory is regulated and accredited by CLIA and the Joint Commission (JCHO) as qualified to perform high-complexity testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. Capstone Healthcare | 8601 Dunwood Place | Building 400 | Suite 444 | Atlanta, GA | 30350 Page 2 of 3 Accession ID: 10000520 Laboratory Director: John Hanson, PhD CLIA ID Number: 11D2073885 C-55 (Comprehensive Panel) SELECTED CITATIONS 1. Azzollini J, Pesenti C, Ferrari L, Fontana L, Calvello M, Peissel B, Portera G, Tabano S, Carcangiu ML, Riva P, Miozzo M, Manoukian S (2017) Revertant mosaicism for family mutations is not observed in BRCA1/2 phenocopies. PLoS One. 2017;12(2):e0171663. Epub 2017 Feb 15 (PMID: 28199346) 2. Crawford B, Adams SB, Sittler T, van den Akker J, Chan S, Leitner O, Ryan L, Gil E, van 't Veer L (2017) Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients. Breast Cancer Res Treat. 2017 Jun;163(2):383-390. Epub 2017 Mar 9 (PMID: 28281021) 3. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917-21 (PMID: 15829967) 4. Hwang SM, Lee KC, Lee MS, Park KU (2017) Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2. Cancer Res Treat. 2018 Jan;50(1):255-264. Epub 2017 Apr 7 (PMID: 28392550) 5. Schenk D, Song G, Ke Y, Wang Z (2017) Amplification of overlapping DNA amplicons in a single-tube multiplex PCR for targeted next-generation sequencing of BRCA1 and BRCA2. PLoS One. 2017;12(7):e0181062. Epub 2017 Jul 12 (PMID: 28704513) 6. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S, Foretova L, Soucek P, King MC (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006 Mar 22;295(12):1379-88 (PMID: 16551709) 7. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21-28;378(6559):789-92 (PMID: 8524414) Capstone Healthcare | 8601 Dunwood Place | Building 400 | Suite 444 | Atlanta, GA | 30350 Page 3 of 3.
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