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CC-SIGN® Targeted Oncology Panel (TOP) by Next-Generation Sequencing

Clinical Updates

New Test: CC-SIGN® Targeted Oncology Panel (TOP) by Next-Generation Sequencing

Available to order starting on June 20, 2023.

A new, enhanced 59-gene hotspot Next-Generation Sequencing (NGS) panel is available for tumor DNA and RNA evaluation.

The Targeted Oncology Panel (TOP) is a custom 59-gene Next-Generation Sequencing (NGS) panel developed for the identification of single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number gains (CNVs) from DNA specimens, and fusion transcripts and aberrant transcripts from RNA specimens.

The workflow allows for the concurrent testing of DNA and RNA to analyze over 1,000 biomarkers.

Targeted Oncology Panel by NGS

Order Codes
TOPTO (FFPE Tissue)
TOPCY (Cytology Alcohol or Formalin fixed cell block)
TOPBM (Bone Marrow Aspirate)
TOPPB (Peripheral Blood)

This test requires 5-10% tumor purity and does not evaluate circulating tumor DNA.

CPT Code
81445

Methodology
Next-Generation Sequencing

Specimen Type
FFPE Tissue
15 charged, unbaked, and unstained slides sectioned at 7 μm.
One pre and one post H&E slide with tumor area circled, and percent rumor indicated.

Cytology
15 charged, unbaked and unstained slides sectioned at 7 μm.
One H&E slide with tumor percent indicated.

Bone Marrow Aspirate
2 mL, Lavender K2EDTA Tube

Peripheral Blood
4 mL, Lavender K2EDTA Tube

Days Performed
2–3 times per week

Turnaround Time
8 days

Overview

Single nucleotide variants (SNVs), small insertions and deletions (indels), copy number gains, select fusions, and aberrant transcripts evaluated by this assay can aid in the diagnostic and therapeutic assessment of a variety of tumor types, including non-small cell lung cancer, melanoma, colorectal cancer, prostate cancer, breast cancer, glioblastoma, thyroid cancer, and others.

This panel can also provide focused tumor profiling for patients with locally advanced/metastatic disease, who are candidates for anti-cancer therapy, to identify uncommon but targetable alterations. In particular, this panel can be utilized for small biopsies and cytology specimens that may not be amenable to more comprehensive genomic sequencing.

Targeted Genes & RNA Fusions

For a full list of targeted genes & RNA fusions, please refer to the Targeted Oncology Panel by Next-Generation Sequencing Technical Brief.

How to Order

Place an order through an electronic interface or complete a Molecular Oncology & Associated Biomarkers Requisition and submit it with the specimen(s).

Hot Spot Panel Discontinuation

The TOP NGS panel will replace solid tumor hotspot mini-panels (Lung, Colorectal, Melanoma, GIST, etc.), as all previously detected biomarkers are included in the new testing.

In situations where the mini-panels were previously used as part of an upfront diagnostic workup, pathologist diagnostic and reflex ordering will utilize TOP testing.

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May 2023: New Test – Clozapine (CLOZA)

Clinical Updates

New Test: Clozapine (CLOZA)

Effective May 23, 2023.

Therapeutic drug monitoring for clozapine will be offered as an in-house test starting Tuesday, May 23, 2023.

The current send-out test, Clozapine and Metabolites, Serum or Plasma, Quantitative (CLOZSP), currently sent out to ARUP Laboratories, will be discontinued on June 20, 2023.

Clozapine (CLOZA)

New Test – CLOZA

Specimen Type
Red Serum Tube (No Additive)

Methodology
Turbidimetric immunoassay

Result Components
Clozapine

Days Performed
Monday – Saturday

Turnaround Time
1-4 days

Clozapine results greater than 1000 ng/mL have been designated as urgent.

Sendout Test – CLOZSP

Specimen Type
Red Serum Tube (No Additive) or Lavender K2EDTA Tube

Methodology
Liquid chromatography-tandem mass spectrometry

Result Components
Clozapine
Norclozapine
Clozapine-N-Oxide

Days Performed
Sunday – Saturday

Turnaround Time
2-4 days

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May 2023: Changes to Legionella Diagnostic Testing (LEGPCR)

Clinical Updates

Changes to Legionella Diagnostic Testing (LEGPCR)

Effective May 2, 2023.

Improvements to Cleveland Clinic Laboratories’ Legionella PCR assay will result in the discontinuation of most Legionella cultures.

Beginning May 2, 2023, Legionella pneumophila PCR (LEGPCR) will include additional DNA targets for Legionella, including species other than Legionella pneumophila, and a target specific for Legionella pneumophila serogroup 1.

This assay design is modeled after the U.S. Centers for Disease Control & Prevention’s assay.1

Legionella pneumophila PCR (LEGPCR)

Specimen Requirements
Lower respiratory samples, including bronchoalveolar lavage (BAL) and sputa, will continue to be the acceptable specimen types for PCR.

Results
Possible interpretations of test results include:

  • Legionella pneumophila Serogroup 1 Detected
  • Legionella pneumophila (not Serogroup 1) Detected
  • Legionella species (not pneumophila) Detected

Additional Updates
Beginning May 23, 2023, routine culture for Legionella spp. (LEGCUL) will be discontinued, but culture will reflexively be performed on any sample with detectable Legionella DNA by PCR.

Note: There is no change to Legionella urine antigen (LEGUAG) testing.

Reference

1 Benitez AJ, Winchell JM. Clinical application of a multiplex real-time PCR assay for simultaneous detection of Legionella species, Legionella pneumophila, and Legionella pneumophila serogroup 1. J Clin Microbiol. 2013 Jan;51(1):348-51. doi: 10.1128/JCM.02510-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536254/pdf/zjm348.pdf

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September 2022: Best Practice for Detecting Hyperhomocysteinemia – Homocysteine Testing—Not MTHFR Genotyping

Best Practice for Detecting Hyperhomocysteinemia: Homocysteine Testing—Not MTHFR Genotyping

There is no conclusive evidence supporting the clinical value of MTHFR polymorphism genotyping.

Practice guidelines from multiple professional societies agree that MTHFR polymorphism genotyping should not be ordered as part of clinical evaluation.

If there is a clinical concern regarding hyperhomocysteinemia, Cleveland Clinic Laboratories recommends Homocysteine testing (HOMCYS) in place of MTHFR genotyping. Homocysteine testing is less expensive, generates a result more quickly, and provides additional actionable information for patient management.

Best Practice

If there is a clinical concern regarding hyperhomocysteinemia (HCC), Cleveland Clinic Laboratories recommends Homocysteine testing (HOMCYS) in place of MTHFR genotyping

Upcoming Changes

November 15, 2022: MTHFR genotyping (MTHFRM) will no longer be available as a send-out test, even if ordered as a miscellaneous test.

March 16, 2021: Homocysteine testing (HOMCYS) will replace MTHFR genotyping at Cleveland Clinic.

Homocysteine (HOMCYS) Test Details

Test Name

Homocysteine

Test Code

CPT Code

83090

Performing Laboratory

Cleveland Clinic Laboratories

FDA Compliance

In Vitro Diagnostic (IVD)

Methodology

Enzymatic

Days Performed

Sun – Sat

Turnaround Time

8 hours

Specimen Requirements

Type:
Plasma

Volume:
1 mL

Specimen Container:
Light Green Lithium Heparin Plasma Separator Tube (PST)

Transport Temperature:
Refrigerated

Place specimen on ice after draw.

Alternative Specimen Requirements

Type:
Serum

Volume:
1 mL

Specimen Container:
Gold Serum Separation Tube (SST)

Transport Temperature:
Refrigerated

Place specimen on ice after draw.

Special Instructions

• Centrifuge and separate plasma/serum from cells less than one hour after collection.

• If collected in a non-gel separator tube, centrifuge and transfer plasma/serum to a CCL tube and refrigerate.

Stability

Ambient:
4 days

Refrigerated:
4 weeks

Frozen:
10 months

Reference Interval

18-99 Years – Normal:
<15.1 umol/L

Lack of Evidence for MTHFR Polymorphism Genotyping

Recommendation: Test Plasma Homocysteine Levels

There is no conclusive evidence supporting the clinical value of MTHFR polymorphism genotyping.

If there is a clinical concern regarding hyperhomocysteinemia, Cleveland Clinic Laboratories recommends Homocysteine (HOMCYS) testing.

• Multiple practice guidelines agree that MTHFR polymorphism genotyping should not be ordered as part of a clinical evaluation.

• A cheaper, faster, and more accurate way to test for hyperhomocysteinemia is to measure plasma homocysteine levels.

• If plasma homocysteine levels are high, patients can supplement with vitamins such as B6, B12, folate, and folic acid.

• If plasma homocysteine levels are normal, no treatment is indicated—even if there is an MTHFR variant.

Plasma homocysteine levels determine clinical management, regardless of the MTHFR genotype result.

After reviewing these guidelines,
Cleveland Clinic’s RT-PLMI Section of Molecular Pathology, Genomic Medicine Institute, and Laboratory Stewardship Committee agreed to discontinue MTHFR polymorphism genotyping.

Background

The MTHFR gene (OMIM: 607093) on 1p36.22 encodes the 5,10-methylenetetrahydrofolate reductase enzyme, which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulatory form of folate. This enzyme is also involved in the metabolism of the amino acid, homocysteine. A deficiency of the enzyme can lead to HHC.

Polymorphisms are common variants within a gene that do not necessarily affect its function, unlike pathogenic or disease-causing variants. Two commonly tested polymorphic variants in MTHFR are:

c.665C>T* (p.Ala222Val)
*Historically referred to as C677T, the ‘thermolabile’ variant

c.1286A>C (p.Glu429Ala)

These variants are so common that approximately 25% of individuals with Hispanic ancestry and 15% of North Americans with European ancestry have two copies of c.665C>T.

The presence of two copies of c.665C>T (homozygosity) may result in decreased MTHFR enzyme activity and mild HHC. Neither of these MTHFR polymorphisms causes severe MTHFR deficiency (<20% enzyme activity).

References

1. Lack of Evidence for MTHFR Polymorphism Testing. ACMG Practice Guideline. Genet Med. 2013;15(2):153-6.
2. Inherited Thrombophilias in Pregnancy. ACOG Practice Bulletin. No. 197. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e18–34.
3. Levin BL, Varga E. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. J Genet Counsel. 2016;25:901-11.
4. Choosing Wisely® Initiative https://www.choosingwisely.org/
5. Eng, C. A Genetic Test You Don’t Need: Testing MTHFR is usually unnecessary. Cleveland Clinic Health Essentials. https://health.clevelandclinic.org/a-genetic-test-you-dont-need/. Accessed November 19, 2020.

Updating Best Practices

Cleveland Clinic Laboratories encourages providers to incorporate Homocysteine testing (HOMCYS) into their practice in place of MTHFR genotyping.

November 15, 2022: MTHFR genotyping will no longer be available as a send-out test, even if ordered as a miscellaneous test.

March 16, 2021: MTHFR genotyping will no longer be performed in-house at Cleveland Clinic.

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September 2021: New Test – Beta(β)-D-Glucan Assay

Clinical Update

New Test: Beta(β)-D-Glucan Assay

In-house Beta(β)-D-Glucan (BDG) testing is now available.

The assay diagnoses certain systemic fungal infections, such as Candidemia, and assists in the prognostication and monitoring response to anti-fungal therapy in hospitalized patients.

This FDA-approved test is a protease zymogen-based colorimetric assay (FUNGITELL® ASSAY) based on a modification of the Limulus Amebocyte Lysate (LAL) pathway in which BDG, where present in the sample, binds Factor G. Activated Factor G turns a proclotting enzyme to clotting enzyme. The latter cleaves an artificial chromogenic substrate (a short peptide) to generate a color. The reaction occurs at 37°C and is kinetically read by a spectrophotometer to generate a standard curve and sample readouts that are subsequently converted to BDG concentrations in pg/ml.

It is important to note that certain fungi, such as the genus Cryptococcus that produces very low levels of BDG, may not result in serum BDG levels sufficiently elevated to be detected by the assay. Infections with fungi of the order Mucorales, such as AbsidiaMucor, and Rhizopus, that are not known to produce BDG can also yield non-detectable serum BDG levels. In addition, the yeast phase of Blastomyces dermatitidis produces little BDG and may not be detected by the assay. Furthermore, positive BDG results have been seen in hemodialysis patients, those who received certain fractionated blood products (such as albumin, IVIg), and those exposed to glucan-containing gauze or surgical sponges.

The sample should be centrifuged within 2 hours of collection to separate the serum from the cells.

Separated samples or serum should be stored refrigerated pending delivery to the testing laboratory.

Heel and fingerprick collections are unacceptable.

Test Name
(1,3) B-D Glucan

Test Code
BDGLUC

CPT Code
87449

Methodology
Protease zymogen-based colorimetric assay (FUNGITELL® ASSAY)

Specimen Requirements
Type: Serum
Volume: 0.5 mL
Container: Gold BD Hemogard™ Serum Separation Tubes (SST)™
Transport Temperature: Refrigerated

Stability
Ambient: Unacceptable
Refrigerated: 7 days
Frozen: 1 year

Reference Range
Negative; <60 pg/mL

Reportable Range
31 to 500 pg/mL

Days Performed
Monday, Wednesday, Friday

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CC-SIGN® Head & Neck Gene Fusion Next-Generation Sequencing Panel

CC-SIGN® Head & Neck Gene Fusion Next-Generation Sequencing Panel

This customized, 30-gene Next-Generation Sequencing (NGS)-based laboratory-developed test is intended for use in the diagnosis and management of benign and malignant tumors of the head and neck.

In particular, salivary gland neoplasms are broadly covered by this panel—which also covers select mesenchymal tumors and other lesions arising in head and neck sites.

The CC-SIGN® Head & Neck Gene Fusion NGS Panel is available as part of a comprehensive, diagnostic consultation or as a stand-alone test. This laboratory-developed test interrogates gene targets associated with known translocations in salivary gland and other solid tumors. Additionally, this panel identifies the corresponding fusion partner which may be helpful in the selection of treatment targets in some cases.

Results are delivered within 14 days of specimen receipt, allowing for a timely, definitive diagnosis in difficult salivary gland tumors and other head and neck lesions in a stand-alone fashion or with the support of our expert pathologists.

Test Overview

Test Name

Head and Neck Next Generation Sequencing (HDNK)

CPT Codes

81445
88381

Turnaround Time

14 days (upon specimen receipt)

Specimen Requirements

Formalin-fixed, paraffin-embedded (FFPE) tissue
• Ten (10) unstained, 4 μM sections of FFPE on charged, unbaked slides
• One (1) H&E stained slide with best tumor area* circled by a pathologist

*minimum of 20% tumor content for best results

Transport Temperature

Room (ambient) temperature

Specimen Shipping Address

Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106

Specimens must be sent via UPS, FedEx, or DHL review our Shipping Information for more details.

Clinical Indications

This test is intended for the diagnosis of benign or malignant mesenchymal tumors (sarcomas & their mimics) as well as other solid tumors.

Targeted Gene Regions

Genes interrogated, including relevant transcripts and exons, are listed in alphabetical order.

A

Gene, Transcript, Exons

ALK
NM_004304
2, 4, 6, 10, 16-23, 25, 26

B

Gene, Transcript, Exons

BRAF
NM_004333
Exons 1-5, 7-16, 18

C

Gene, Transcript, Exons

CAMTA1
NM_015215
Exons 3, 8-10

CRTC1
NM_015321
Exons 1-4

E

Gene, Transcript, Exons

ETV6
NM_001987
Exons 1-7

EWSR1
NM_005243
Exons 4-14

F

Gene, Transcript, Exons

FOS
NM_005252
Exon 4

FOSB
NM_006732
Exons 1, 2

FOXO1
NM_002015
Exons 1-3

FUS
NM_004960
Exons 3-11, 13, 14

G

Gene, Transcript, Exons

GLI1
NM_005269
Exons 4-7

H

Gene, Transcript, Exons

HMGA2
NM_003483
Exons 1-5

M

Gene, Transcript, Exons

MAML2
NM_032427
Exons 2, 3

MKL2
NM_014048
Exons 11-13

MYB
NM_001130173
Exons 7-9, 11-16

N

Gene, Transcript, Exons

NCOA1
NM_147223
Exons 12-15

NR4A3
NM_006981
Exon 2

NR4A3
NM_173200
Exons 3, 4

NTRK1*
NM_002529
Exons 2, 4, 6, 8, 10-14

NTRK2*
NM_006180
Exons 5, 7, 9, 11-18

NTRK3*
NM_001007156
Exon 15

NTRK3*
NM_002530
Exons 4, 7, 10, 12-16

NUTM1
NM_175741
Exons 2-4, 6

*A specimen positive for a fusion in one of these genes makes the patient a candidate for larotrectinib treatment.
Standalone NTRK testing is also available via the CC-SIGN® NTRK Gene Fusion NGS Panel.

P

Gene, Transcript, Exons

PAX3
NM_181459
Exons 6-8

PAX7
NM_002584
Exons 6-8

PLAG1
NM_002655
Exons 1-4

PRKD1
NM_002742
Exons 10-13

R

Gene, Transcript, Exons

RET
NM_020630
Exons 2, 4, 6, 11, 15, 16

RET
NM_020975
Exons 8-14

S

Gene, Transcript, Exons

SS18
NM_001007559
Exons 2-6, 8-11

SS18
NM_005637
Exons 2, 3

STAT6
NM_001178078
Exons 1-7, 15-20

T

Gene, Transcript, Exons

TFE3
NM_006521
Exons 2-8

Y

Gene, Transcript, Exons

YAP1
NM_001130145
Exons 1-9

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CC-SIGN® NTRK Plus Gene Fusion Next-Generation Sequencing Panel

CC-SIGN® NTRK Gene Fusion Next-Generation Sequencing Panel

This NGS-based laboratory-developed test is designed to detect fusion events in NTRK1, NTRK2, and NTRK3, regardless of fusion partner.

Clinical information obtained from the CC-SIGN® NTRK Gene Fusion NGS Panel can determine if a patient is a candidate for TRK tyrosine kinase inhibitor treatment.

The US Food and Drug Administration (FDA) has approved the use of first-generation TRK tyrosine kinase inhibitors—including larotrectinib (Vitrakvi®) and entrectinib (Rozlytrek®)—to treat patients whose tumors harbor NTRK1, NTRK2, or NTRK3 fusions.

NTRK Fusions are Clinically Actionable

TRK tyrosine kinase inhibitors, such as larotrectinib and entrectinib, are drugs utilized to treat solid tumors with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. These drugs provide a treatment option to patients with no satisfactory alternative therapies or whose cancer has progressed following treatment, specifically in cases that are either metastatic or where surgical resection is likely to result in severe morbidity.1,2 This treatment targets cancers with NTRK fusions and is not limited by tissue or tumor type.

1. U.S. Food & Drug Administration. FDA approves larotrectinib for solid tumors with NTRK gene fusions. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626720.htm. [Online]  Updated Dec 17, 2018.
2. U.S. Food & Drug Administration. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinibntrk-solid-tumors-and-ros-1-nsclc [Online] Updated Aug 16, 2019.

Test Overview

Test Name

NTRK Gene Fusion NGS Panel (NTRK)

CPT Codes

81445, 88381

Turnaround Time

14 days (upon specimen receipt)

Specimen Requirements

Please include the original pathology report with any submitted specimens.

Ten (10) unstained, 4 µM sections of formalin-fixed, paraffin-embedded (FFPE) on charged, unbaked slides

One H&E stained slide with best tumor area circled by a pathologist (minimum of 20% tumor content for best results)

Transport Temperature

Room (ambient) temperature

Specimen Mailing Address

Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106

Specimens must be sent via UPS, FedEx, or DHL review our Shipping Information for more details.

Clinical Indications

This test is intended for determining NTRK gene fusion status to identify candidates for larotrectinib treatment.

Limitations

This test does not detect single nucleotide variants; some data show acquired kinase domain resistance mutations that are not interrogated by this test.

Interrogated Genes

NTRK1
NM_002529
Exons 2, 4, 6, 8, 10-14

NTRK2
NM_006180
Exons 5, 7, 9, 11-18

NTRK3
NM_001007156
Exon 15

NTRK3
NM_002530
Exons 4, 7, 10, 12-16

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CC-SIGN® Solid Tumor Gene Fusion Next-Generation Sequencing Panel

CC-SIGN® Solid Tumor Gene Fusion Next-Generation Sequencing Panel

This customized, 59-gene Next-Generation Sequencing (NGS)-based laboratory-developed test is intended for use in the diagnosis and management of benign and malignant mesenchymal tumors (sarcomas and their mimics) as well as other solid tumors.

The CC-SIGN® Solid Tumor Gene Fusion NGS Panel is available as part of a comprehensive, diagnostic consultation or as a stand-alone test. This laboratory-developed test interrogates gene targets associated with known translocations in mesenchymal and other solid tumors. Additionally, this panel identifies the corresponding fusion partner and predicted exon breakpoints, which can be of diagnostic and prognostic significance. Fluorescence in situ hybridization-based testing is available for specific fusion questions.

Results are delivered within 14 days of specimen receipt, allowing for a timely, definitive diagnosis in difficult sarcoma and solid tumor cases in a stand-alone fashion or with the support of our expert pathologists.

Test Overview

Test Name

Solid Tumor Gene Fusion NGS Panel (SRCNGS)

CPT Codes

81445
88381

Turnaround Time

14 days (upon specimen receipt)

Specimen Requirements

Formalin-fixed, paraffin-embedded (FFPE) tissue
• Ten (10) unstained, 4 μM sections of FFPE on charged, unbaked slides
• One (1) H&E stained slide with best tumor area* circled by a pathologist

*minimum of 20% tumor content for best results

Transport Temperature

Room (ambient) temperature

Specimen Shipping Address

Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106

Specimens must be sent via UPS, FedEx, or DHL review our Shipping Information for more details.

Clinical Indications

This test is intended for the diagnosis of benign or malignant mesenchymal tumors (sarcomas & their mimics) as well as other solid tumors.

Targeted Gene Regions

Genes interrogated, including relevant transcripts and exons, are listed in alphabetical order.

A

Gene, Transcript, Exons

ABL1
NM_004304
2, 4, 6, 10, 16-23, 25, 26

B

Gene, Transcript, Exons

BCOR
NM_001123385
Exons 3-8, 12, 14, 15

BCOR
NM_017745
Exon 8

BRAF
NM_004333
Exons 1-5, 7-16, 18

C

Gene, Transcript, Exons

CAMTA1
NM_015215
Exons 3, 8-10

CCNB3
NM_033031
Exons 2-6

CIC
NM_015125
Exons 12, 17-20

CRTC1
NM_015321
Exons 1-4

CSF1
NM_000757
Exons 5-8

CSF1
NM_172212
Exon 9

E

Gene, Transcript, Exons

EPC1
NM_025209
Exons 9-11

ETV6
NM_001987
Exons 1-7

EWSR1
NM_005243
Exons 4-14

F

Gene, Transcript, Exons

FOS
NM_005252
Exon 4

FOSB
NM_006732
Exons 1, 2

FOXO1
NM_002015
Exons 1-3

FUS
NM_004960
Exons 3-11, 13, 14

G

Gene, Transcript, Exons

GLI1
NM_005269
Exons 4-7

H

Gene, Transcript, Exons

HMGA2
NM_003483
Exons 1-5

J

Gene, Transcript, Exons

JAZF1
NM_175061
Exons 2-4

M

Gene, Transcript, Exons

MAML2
NM_032427
Exons 2, 3

MEAF6
NM_001270875
Exons 4, 5

MKL2
NM_014048
Exons 11-13

MYB
NM_001130173
Exons 7-9, 11-16

N

Gene, Transcript, Exons

NCOA1
NM_147223
Exons 12-15

NCOA2
NM_006540
Exons 11-16

NCOA3
NM_006534
Exons 2, 13-16

NCOA3
NM_181659
Exon 20

NOTCH1
NM_017617
Exons 2, 4, 24-31

NOTCH2
NM_024408
Exons 5-7, 24-29

NOTCH3
NM_000435
Exons 25-30

NR4A3
NM_006981
Exon 2

NR4A3
NM_173200
Exons 3, 4

NTRK1*
NM_002529
Exons 2, 4, 6, 8, 10-14

NTRK2*
NM_006180
Exons 5, 7, 9, 11-18

NTRK3*
NM_001007156
Exon 15

NTRK3*
NM_002530
Exons 4, 7, 10, 12-16

NUTM1
NM_175741
Exons 2-4, 6

*A specimen positive for a fusion in one of these genes makes the patient a candidate for larotrectinib treatment.
Standalone NTRK testing is also available via the CC-SIGN® NTRK Gene Fusion NGS Panel.

P

Gene, Transcript, Exons

PAX3
NM_181459
Exons 6-8

PAX7
NM_002584
Exons 6-8

PDGFB
NM_002608
Exons 2, 3

PDGFD
NM_025208
Exons 5-7

PGR
NM_000926
Exons 1-3

PHF1
NM_024165
Exons 1, 2, 10-12

PLAG1
NM_002655
Exons 1-4

PRDM10
NM_199437
Exons 12, 13

PRKD1
NM_002742
Exons 10-13

R

Gene, Transcript, Exons

RAF1
NM_002880
Exons 4-12

RELA
NM_021975
Exons 3 , 4, 11

RET
NM_020630
Exons 2, 4, 6, 11, 15, 16

RET
NM_020975
Exons 8-14

ROS1
NM_002944
2, 4, 7, 31-38

S

Gene, Transcript, Exons

SRF
NM_003131
Exons 2-4

SS18
NM_001007559
Exons 2-6, 8-11

SS18
NM_005637
Exons 2, 3

STAT6
NM_001178078
Exons 1-7, 15-20

T

Gene, Transcript, Exons

TAF15
NM_139215
Exons 5-7

TCF12
NM_207036
Exons 4-6

TFE3
NM_006521
Exons 2-8

TFEB
NM_007162
Exons 1-4, 9

TFG
NM_006070
Exons 3-7

TRIM11
NM_145214
Exons 2, 3

U

Gene, Transcript, Exons

USP6
NM_004505
Exons 1-3

W

Gene, Transcript, Exons

WWTR1
NM_015472
Exons 3, 4

Y

Gene, Transcript, Exons

YAP1
NM_001130145
Exons 1-9

YWHAE
NM_006761
Exon 5

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Updates to Cystic Fibrosis Pathogenic Variant Analysis Testing

New & Updated Tests

Updates to Cystic Fibrosis Pathogenic Variant Analysis (CFMDX) Testing

As of November 27, 2018, Cleveland Clinic Laboratories’ Cystic Fibrosis Carrier Screening and Diagnosis laboratory developed test has been updated with several new features.

The updated version of this test includes all 23 variants recommended for universal screening by the American College of Medical Genetics and Genomics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG), as well as all variants included in the Ohio Newborn Screening Panel.

Additional changes include:

• The total number of variants, both observable and reportable, will increase from 139 to 142.

• Additionally, the mutation detection method will change, resulting in a decreased test price.

• Turnaround time for testing will remain at 10 days.

• The new report includes a table of known detection rates and residual carrier risk based on ethnicity.

Testing Details

Test Name:

Cystic Fibrosis Pathogenic Variant Analysis (CFMDX)

CPT Code:

81220

Turnaround Time:

10 Days

Specimen Requirements:

Indications for Use:

• General population cystic fibrosis carrier screening in all ethnicities
• Carrier screening for patients with known family history of cystic fibrosis
• Carrier screening in partners of known cystic fibrosis carriers
• Abnormal newborn screen confirmation of CFTR variant(s)
• Molecular testing of patients with suspected cystic fibrosis

Legacy names of the 142 pathogenic variants and 3 conditionally-reported variants are listed below in alphabetical order:

1

1078delT

1154insTC

1213delT

1248+1G>A

1259insA

1341+1G>A

1461ins4

1525-1G>A

1548delG

1677delTA

1717-1G>A

1717-8G>A

1811+1.6kbA>G

1812-1G>A

1898+1G>A

1898+3A>G

1898+5G>A

1898+5G>T

2

2055del9>A

2143delT

2183AAtoG

2184delA

2184insA

2307insA

2347delG

2585delT

2622+1G>A

2711delT

2789+5G>A

3

394delTT

3007delG

3120+1G>A

3120G>A

3121-1G>A

3199del6

3272-26A>G

3659delC

3791delC

3849+10KbC>T

3876delA

3905insT

4

405+1G>A

406-1G>A

4005+1G>A

4016insT

4209TGTT>AA

4382delA

457TAT>G

5

574delA

6

621+1G>T

663delT

7

711+1G>T

711+3A>G

711+5G>A

712-1G>T

8

852del22

9

935delA

A

A455E

A559T

C

CFTRdele2,3

CFTRdele22,23

D

D110H

D1152H

deltaF508

deltaI507

E

E1104X

E585X

E60X

E822X

E831X

E92K

E92X

F

F508C

G

G1244E

G1349D

G178R

G330X

G542X

G551D

G85E

G970R

H

H199Y

I

I336K

K

K710X

L

L1065P

L1077P

L206W

L467P

L732X

L927P

M

M1101K

M1V

N

N1303K

P

P205S

P67L

Q

Q1313X

Q220X

Q39X

Q493X

Q525X

Q552X

Q890X

Q98X

R

R1066C

R1066H

R1158X

R1162X

R117C

R117H

R334W

R347H

R347P

R352Q

R553X

R560K

R560T

R709X

R75X

R764X

R851X

S

S1196X

S1251N

S1255X

S341P

S466X

S489X

S492F

S549N

S549R-CGT

S549R-AGG

S945L

T

T338I

V

V520F

W

W1089X

W1204X (3611)

W1204X (3612)

W1282X

W401X

W846X

Y

Y1092X

Y1092X

Y122X

Conditionally Reported:

Poly T

I506V

I507V

Posted on

October 2018: Updates to Fecal Calprotectin (CALPRO) Testing

Effective October 16, 2018, Fecal Calprotectin (CALPRO) testing will be performed within Cleveland Clinic’s Microbiology Section.

The quantitative detection of calprotectin is an in vitro diagnostic test to aid in the diagnosis of inflammatory bowel disease (IBD) in conjunction with other clinical and laboratory findings.

Fecal calprotectin is an indicator of neutrophils in the stool and is not specific for IBD. Elevations in fecal calprotectin may be caused by proton pump inhibitors, non-steroid-anti-inflammatory-drugs, and intestinal impairments other than IBD (e.g., diverticulitis, celiac disease, infections, cancer).

Preserved stool specimens cannot be accepted.

Specimen Information

Specimen Type:
Unpreserved stool

Collection Container:
Sterile Specimen Container

Reference Ranges

Normal:
<50 mg/kg

Borderline:
50-120 mg/kg

Abnormal:
>120 mg/kg

Reporting Range:
27.1 to 3000 mg/kg

Methodology

QUANTA Lite® Extended Range ELISA (FDA-approved)

Limitations

Calprotectin results generated by the FDA-approved QUANTA Lite Extended Range Assay cannot be directly compared to those determined by other methods.

Any additional information will be included in a future Technical Update.  If you have any questions about these changes, please contact Client Services for assistance.