XTAG CYSTIC FIBROSIS 39 KIT V2, (CFTR 39 KIT V2), MODEL I027C0231, I027D0266, I027E0267

K083846 · Luminex Molecular Diagnostics, Inc. · NUA · Sep 1, 2009 · Immunology

Device Facts

• Record ID: K083846
• Device Name: XTAG CYSTIC FIBROSIS 39 KIT V2, (CFTR 39 KIT V2), MODEL I027C0231, I027D0266, I027E0267
• Applicant: Luminex Molecular Diagnostics, Inc.
• Product Code: NUA · Immunology
• Decision Date: Sep 1, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5900
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The xTAG™ Cystic Fibrosis 39 Kit v2 is a device used to simultaneously detect and identify a panel of mutations and variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in human blood specimens. The panel includes mutations and variants currently recommended by the American College of Medical Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG) plus some of the world's most common and North American prevalent mutations. The xTAG™ Cystic Fibrosis 39 Kit v2 is a qualitative genotyping test which provides information intended to be used for carrier testing in adults of reproductive age, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children. The kit is not indicated for use in fetal diagnostic or pre-implantation testing. This kit is also not indicated for stand-alone diagnostic purposes.

Device Story

The xTAG Cystic Fibrosis 39 kit v2 is an in vitro diagnostic test for detecting 39 CFTR gene mutations and 4 variants in human whole blood. The process involves multiplex PCR amplification of CFTR gene segments, followed by multiplex allele-specific primer extension (ASPE) using primers with unique 5' tags. These tagged primers hybridize to complementary sequences on spectrally distinguishable polystyrene beads. A biotinylated reporter molecule (streptavidin-phycoerythrin) binds to the extended primers. The Luminex 100 or 200 instrument uses two lasers to identify the bead (genotype) and the presence of the reporter (allele detection). The xTAG Data Analysis Software (TDAS) processes the MFI signals to provide a qualitative genotype. The device is used in clinical laboratories by trained personnel. Results assist clinicians in carrier screening and diagnostic confirmation of cystic fibrosis. The device provides a standardized, high-throughput method for identifying common CFTR mutations, facilitating timely clinical decision-making and patient management.

Clinical Evidence

Bench testing only. Accuracy assessed using 319 samples (clinical specimens, cell lines, plasmids) confirmed by bi-directional sequencing; 100% agreement with predicate. Precision/reproducibility evaluated across 3 sites, 3 lots, and multiple operators; >99.54% precision. LoD established at 1.56 ng/µL. Interference testing showed no significant inhibition by hemoglobin, bilirubin, or triglycerides.

Technological Characteristics

Multiplex PCR and Allele Specific Primer Extension (ASPE) assay. Uses polystyrene beads internally dyed with red/infrared fluorochromes. Analyzed on Luminex 100/200 flow cytometry-based platform. Software-based genotype calling. Requires PCR thermal cycler and Luminex instrument. Reagents include Platinum TFI DNA Polymerase, Shrimp Alkaline Phosphatase, and Exonuclease I.

Indications for Use

Indicated for carrier testing in adults of reproductive age, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children. Not for fetal diagnostic, pre-implantation, or stand-alone diagnostic use.

Regulatory Classification

Identification

The CFTR gene mutation detection system is a device used to simultaneously detect and identify a panel of mutations and variants in the CFTR gene. It is intended as an aid in confirmatory diagnostic testing of individuals with suspected cystic fibrosis (CF), carrier identification, and newborn screening. This device is not intended for stand-alone diagnostic purposes, prenatal diagnostic, pre-implantation, or population screening.

Special Controls

*Classification.* Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: CFTR Gene Mutation Detection System.” See § 866.1(e) for the availability of this guidance document.

Predicate Devices

• xTAG™ Cystic Fibrosis Kit (k043011, k060627)

Submission Summary (Full Text)

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K0r3846

# 510(K) SUMMARY

## Cystic Fibrosis 39 kit v2

SEP - 1 2009

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirement of 21 CFR 807.92.

510(k) Number: k083846

Purpose for Submission: New Device.

Measurand: CFTR (cystic Fibrosis transmembrane conductance regulator) gene from human blood specimens

Type of Test: Qualitative nucleic acid multiplex test.

#### Applicant:

Luminex Molecular Diagnostics Inc. 439 University Ave. Toronto, ON M5G 1Y8 Canada Tel: [phone] x374 Fax: [phone] Contact person: Gloria Lee

Proprietary and Established Names: xTAG® Cystic Fibrosis 39 kit v2

#### Regulatory Information:

1. Regulation Section:
21 CFR 866.5900, CFTR (cystic fibrosis transmembrane conductance regulator) gene mutation detection system

2. Classification: Class 11

3. Product Code: NUA

4. Panel: lmmunology (82)

510(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.

Page 1 of 13

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#### Intended Use :

The xTAG® Cystic Fibrosis 39 kit v2 is a device used to simultaneously detect and identify a panel of mutations and variants in the cystic fibrosis transmembrance regulator (CFTR) gene in human blood specimens. The panel includes mutations and variants currently recommended by the American College of Medical Genetics and American College of Obstetricians and Gynecologists (ACMG/ACOG), plus some of the worlds most common and North Americanprevalent mutations. The xTAG Cystic Fibrosis 39 kit v2 is a qualitative genotyping test which provides information intended to be used for carrier testing in adults of reproductive age, as an aid in newborn screening, and in confirmatory diagnostic testing in newborns and children.

The kit is not indicated for use in fetal diagnostic or pre-implantation testing. This kit is also not indicated for stand-alone diagnostic purposes.

| ΔF508* | 1717-1G>A* | W1282X* | 2307insA |
|-----------|---------------|-----------|----------|
| ΔI507* | R560T* | 1078delT | Y1092X |
| G542X* | R553X* | 394delTT | M1101K |
| G85E* | G551D* | Y122X | S1255X |
| R117H* | 1898+1G>A* | R347H | 3876delA |
| 621+1G>T* | 2184delA* | V520F | 3905insT |
| 711+1G>T* | 2789+5G>A* | A559T | 5/7/9T |
| N1303K* | 3120+1G>A* | S549N | F508C |
| R334W* | R1162X* | S549R | I507V |
| R347P* | 3659delC* | 1898+5G>T | I506V |
| A455E* | 3849+10kbC>T* | 2183AA>G | |

Mutations (asterisk denotes ACMG/ACOG panel) and 4 variants (variants italized) included in the xTAG CFTR 39 kit v2

Indication(s) for use; The xTAG Cystic Fibrosis 39 kit v2 is a genotyping test indicated in adults for detecting mutations in the CFTR gene and in newborns and children as an aid in the diagnosis of suspected cystic fibrosis.

Special conditions for use statement(s);

A455E*

The kit is not indicated for use in fetal diagnostic or pre-implantation testing. This kit is also not indicated for standalone diagnostic purposes.

Special instrument requirements:

Luminex 100 or 200 instrument

#### Device Description:

The xTAG CFTR 39 kit v2 includes the following components:

3849+10kbC>T*

- PCR Primer Mix v2 including dNTPs designed to simultaneously produce 23 amplimers of the CFTR gene (24 in the presence of CFTR del 2, 3).
- ASPE Mix A v2 including dNTPs contains primers designed to hybridize to either wild-type or mutant alleles ◆ with proprietary sequences at their 5' ends designed to specifically hybridize to complementary sequences coupled to a given bead population in Bead Mix A.
- Bead Mix A v2 contains spectrally distinguishable populations of polystyrene beads internally dyed with red and . infrared fluorochromes coupled to proprietary DNA sequences designed to specifically hybridize to complementary sequences on the ASPE primers in ASPE Mix A v2.
- 10X Buffer

510(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.

Page 2 of 13

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- Platinum® TFI DNA Polymerase .
- Platinum® TFI Reaction Buffer .
- TFI MgCl2 .
- Shrimp Alkaline Phosphatase .
- Exonuclease I .
- Strepavidin-Phycoerythrin Conjugate .
- xTAG Data Analysis Software (TDAS) CFTR .

# Substantial Equivalence Information:

I. Predicate device name(s):
xTAG® Cystic Fibrosis Kit

2. Predicate S10(k) number(s): k043011, k060627

3. Comparison with predicate:

| Parameter | xTAG Cystic Fibrosis 39 kit v2 | xTAG Cystic Fibrosis Kit |
|------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The xTAG Cystic Fibrosis 39 kit v2 is a device used to<br>simultaneously detect and identify a panel of mutations<br>and variants in the cystic fibrosis transmembrane<br>conductance regulator (CFTR) gene in human blood<br>specimens. The panel includes mutations and variants<br>currently recommended by the American College of<br>Medical Genetics and American College of Obstetricians<br>and Gynecologists (ACMG/ACOG), plus some of the<br>worlds most common and North American-prevalent<br>mutations. | The xTAG Cystic Fibrosis Kit is a device used<br>to simultaneously detect and identify a panel<br>of mutations and variants in the cystic fibrosis<br>transmembrane conductance regulator (CFTR)<br>gene in human blood specimens. The panel<br>includes mutations and variants currently<br>recommended by the American College of<br>Medical Genetics and American College of<br>Obstetricians<br>and<br>Gynecologists<br>(ACMG/ACOG), plus some of the worlds<br>most common and North American-prevalent<br>mutations. |
| Indications<br>for Use | The xTAG Cystic Fibrosis 39 kit v2 is a qualitative<br>genotyping test which provides information intended to<br>be used for carrier testing in adults of reproductive age,<br>as an aid in newborn screening, and in confirmatory<br>diagnostic testing in newborns and children. | The xTAG Cystic Fibrosis Kit is a qualitative<br>genotyping test which provides information<br>intended to be used for carrier testing in adults<br>of reproductive age, as an aid in newborn<br>screening, and in confirmatory diagnostic<br>testing in newborns and children. |
| Contra-<br>Indications | The kit is not indicated for use in fetal diagnostic or pre-<br>implantation testing. This kit is also not indicated for<br>stand-alone diagnostic purposes. | The kit is not indicated for use in fetal<br>diagnostic or pre-implantation testing.<br>This<br>kit is also not indicated for stand-alone<br>diagnostic purposes. |
| Type of Test | Multiplex PCR followed by multiplex allele specific<br>primer extension for genotyping, hybridized to multiplex<br>fluorescent microparticles, detected by flow cytometry | Multiplex PCR followed by multiplex allele<br>specific primer extension for genotyping,<br>hybridized to multiplex fluorescent<br>microparticles, detected by flow cytometry. |
| Product<br>Description | Tests for 39 mutations and 4 variants in the CFTR gene<br>(23 of which are recommended by ACMG/ ACOG). The<br>mutations and variants are the same as those tested for<br>by the predicate device | Tests for 39 mutations and 4 variants in the<br>CFTR gene (23 of which are recommended by<br>ACMG/ ACOG). |

510(k) summary for xTAG® CFTR 39 kit v2
Luminex Molecular Diagnostics Inc.

Page 3 of 13

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| Specimen<br>Type | Peripheral human whole blood. | | | | Peripheral human whole blood. | | | |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|-----------|----------|-----------------------------------------------------------------------------|--------------|-----------|----------|
| Instrument<br>System | Luminex 100 or 200 IS | | | | Luminex 100 or 200 IS | | | |
| Software | TDAS CFTR contains 1 template to detect for<br>mutations. Software masking function where user can<br>chose to display results for only the ACMG / ACOG<br>23 mutations or the full panel of mutations. | | | | TDAS CF-I contains 1 template to detect for 39<br>mutations and 4 variants. | | | |
| Mutations<br>Detected | ΔF508 | 1717-1G>A | W1282X | 2307insA | ΔF508 | 1717-1G>A | W1282X | 2307insA |
| | ΔI507 | R560T | 1078delT | Y1092X | ΔI507 | R560T | 1078delT | Y1092X |
| | G542X | R553X | 394delTT | M1101K | G542X | R553X | 394delTT | M1101K |
| | G85E | G551D | Y122X | S1255X | G85E | G551D | Y122X | S1255X |
| | R117H | 1898+1G>A | R347H | 3876delA | R117H | 1898+1G>A | R347H | 3876delA |
| | 621+1G>T | 2184delA | V520F | 3905insT | 621+1G>T | 2184delA | V520F | 3905insT |
| | 711+1G>T | 2789+5G>A | A559T | 5/7/9T | 711+1G>T | 2789+5G>A | A559T | 5/7/9T |
| | N1303K | 3120+1G>A | S549N | F508C | N1303K | 3120+1G>A | S549N | F508C |
| | R334W | R1162X | S549R | I507V | R334W | R1162X | S549R | I507V |
| | R347P | 3659delC | 1898+5G>T | I506V | R347P | 3659delC | 1898+5G>T | I506V |
| | A455E | 3849+10kbC>T | 2183AA>G | | A455E | 3849+10kbC>T | 2183AA>G | |

#### Standard/Guidance Document Referenced (if applicable):

- American College of Medical Genetics (ACMG) / American College of Obstetricians and Gynecologists Technical Standards and Guidelines for CFTR Mutation Testing and Standards and Guidelines for Clinical Genetic Laboratories
- Cystic Fibrosis Foundation / Center for Disease Control Recommendations on Newborn Screening for CF
- FDA Class II Special Controls Guidance: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays (Jan 2007)
- FDA Class II Special Controls Guidance: CFTR Gene Mutation Detection Systems (Oct 2005)
- CDRH Draft Guidance on Multiplex Tests for Heritable DNA Markers, Mutations and Expression Patterns (Feb 2003) CDRH Draft Guidance on Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests (Mar 2003)

CDRH Guidance for the Content of Pre-Market Submission for Software Contained in Medical Devices (May 1998)

- CDRH Guidance on General Principles of Software Validation (Jan 2002)
- CDRH Guidance on Format for Traditional and Abbreviated 510ks (Aug 2005)

MM01-A2: Molecular Diagnostic Methods for Genetic Diseases

- MM13-PE: Collection, Transport, Preparation, and Storage of Specimens for Molecular Methods
- MM17-A: Verification and Validation of Multiplex Nucleic Acid Assays
- EP05-A2: Evaluation of Precision Performance of Clinical Chemistry Devices

EP07-A2E: Interference Testing in Clinical Chemistry

- EP12-A: User Protocol for Evaluation of Qualitative Test Performance
- EP17-A: Protocols for Determining Limits of Detection and Limits of Quantitation

#### Test Principle:

The xTAG CFTR 39 kit v2 incorporates multiplex Polymerase Chain Reaction (PCR) and multiplex Allele Specific Primer Extension (ASPE) with LMD's proprietary Universal Tag sorting system on the Lumines " 100 or 200 xMAP" platorm.

The amplimer sizes range from 179 bp to 465 bp. A multiplex PCR reaction is carried out under optimized conditions. Each sample then undergoes a multiplex allele specific primer extension where an aliquot of the PCR product is run through ASPE A reaction. The ASPE step allows for detection of each allele (wild-type or mutan) of a

510(k) summary for xTAG® CFTR 39 kit v2 Lumines Molecular Diagnostics Inc.

Page 4 of 13

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given locus using an allele-specific probe (ASP) which contains a unique DNA sequence (tag) at its 5' end. Each bi-allelic locus has two ASPs and each tri-allelic loci has 3 ASPs included in the ASPE Mix. For each ASP, the 3 end of the primer is a perfect match for its allele, but will have a 3' mismatch on any other allele. Both these ASPs however are tagged with a common tag at their 5' cnd. The DNA polymerase will only extend the is a perfect match on the 3' end, so that the primer is only extended if its target allele is present in the sample. Biotin-dCTP is incorporated into the extending chain if extension occurs.

For the hybridization reaction product is added directly to microwells containing aliquots of the Bead Mix A v2. Each coupled bead is spectrally distinguishable from the other coupled beads in a given bead mix. A fluorescent reporter molecule (streptaviding) is bound to the biotin on the extended primers. Each agged primer hybridizes only to its unique anti-ag complement; therefore, each colored bead represents a specific allele, through the bead/anti-lag/tagged primer association. The beads are then analyzed by the Luminex The Lumines instrument contains two lasers: one identifies the color-coded bead, and the other identifies the presence of extended allele specific primer through the phycoerythrin reporter. Thus, the genotype of that locus is identified by the presence of phycoerythrin signal attached to one or both ASPs.

For each sample analyzed by the xTAG Cystic Fibrosis 39 kit v2, an output file containing MFI signals from the Luminex instrument is generated. The proprietary software component of this output data file to provide a final qualitative genotype for the sample. The user must select between 2 options for the final output prior to running the assay:

Option 1: Full Panel (39 mutations/deletions + 4 variants). Option 2: ACMG/ACOG panel (23 mutations and deletions).

#### Performance Characteristics (if/when applicable):

## Clinical Performance Characteristics:

a) Method Comparison Studies | Accuracy:

Accuracy of the xTAG CFTR 39 kit v2 was assessed through evaluation of samples representing all alleles (mutations and polymorphisms) probed by the assay. The majority of samples consisted of left-over, anonymized, banked whole-blood specimens. These specimens were supplemented with genomic DNAs from EBV-transformed lymphoid cell lines, and several custom-designed plasmids engineered to contain 1-2 CFTR mutations each. Archived clinical genomic DNA samples were obtained from a variety of sources.

The FDA cleared xTAG Cystic Fibrosis Kit (k043011 and k060627) was used as the comparator for all clinical specimens.

#### 510(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.

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| | ci 14<br>01 85<br>EB | 15.81 1 | 11:15:81 17 | - 90 51 హ | - 15 61 - 1 | 2 54.07 16 | 29.24 11 | - 3-24 - 2 | ﺔ 2017-02-24 11:22:24 | 154.07.20 | 39.76 - | 9.24 12 | 66.37 km 66.37 km | 97 87 - 1 | 15 815 | のお得なのです<br>17:47:82 11 | 175 29 11 | 15.81 | - 27.82 1 | 473.54 13 | ് ജന്മം | - 29 元 中 | : | |
| After allowable re-run and a for | Final %<br>Accuracy Accuracy Accuracy<br>40 3<br>Repear<br>ី | 100.00 - | 100.00 1<br>ర్లు ప్రసిద్ధి ప్రసిద్ధి ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ఆరోగ్య కేంద్రం, ప్రాథమిక ఆరోగ్య కేంద్రం, ప్రాథమిక<br>ーディ<br>តែ | - 00 00 -<br>- 2018-7 | ้างอิง ตัวเล่<br>1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 -<br>,部落 | 100.00<br>ישורים יום יותר | 12.00<br>ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺎ | 100 000<br>新闻网 | מחמש מ<br>的一个 | ្រី | 100.00<br>13 - 10 - 10 -<br>,一直一直 | 1984 1999<br>100 80 | 人 最新 | 00<br>ម្រាប់ប្រជាជាបា<br>EUTFB | 100.00<br>0 0 4 1 | 1100000<br>2017-09-09 11:40:00 | 100 ตุลา อ<br>100 000<br>,在线 | 100.00 -<br>לייני מיני מיני או | 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000<br>STIDENDERS<br>: 上一 | 100.00 1<br>ransar ke | 100.00<br>2017 | ้า - 10 - 100.00 - | 180:00<br>်ရေးနှင့် မြို့နယ်ရှိ ရွာများ | |
| | Total no al Total no al Tre<br>មានក្រុមព្រំ ថា កំណត់ ១០គែល ១០គែល | 发行业<br>ﻟﻠﻌﺐ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ | មួយប្រទេស ស្រ | 200000 - 8- 0 - 0 - 0 - 2 - | 的一个 | 1500 Co | ﻟﻠﻘﻀﺎﺀ ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤ | 新闻网 昨天21: | ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ | 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | ,一 | Comment<br>1990 - "S | 的一个 | 100.00 - 100.00 11 | ,都 | 12 | יים מיני מ | 部指數 | - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - | la volta | ം കോലിക്കും. അവലംബം | 的一个人 | ando a v | |
| ﺗ ﻊ ﺍﻟﻌﺮﺑﻲ ﻭ | | 100:00 | ക്കുവായിരു | | 100 100 00 | 1000 | | 机 - 100.00 | 100.00 | | 39.76 - 100.00 | 100.00 | 100.0 | | 100.00 | 47.82 100.00 | 75 29 - 100 00 | 15.81/5/100.00 | 00 00:00 | | | -29-24 - 100.00 | 2 39.76 - 100.00 | |
| | Total no. af | 100.00 12 15.81 | 1581 | 90.51 - | :15.81 - 1 | 54 07 - 54 07 | 2017 - 29:24 PM | 1329 24 | 29:24 29:24 29:24 | 중앙 54.07 - 3 | | 29.24 | 一66:37 10: | 97.87 - | 15.81. 81 | | | | 47.82 | 100.00 100.00 73.54 2017 100.00 | 0 0 1 2 0 0 100.00 100.00 69.04 100.00 | | | |
| Before allowable retrunn | | | 1100:00 :<br>: | 100.00 | 20100.00 | 100.00 | יינו | 100000 | 10000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | : 100.00 - 1 | 100:00 | ,这<br>100:00<br>.<br>なる。 | ల్లా రాజార్లు<br>100:0 | 100.00 1 | 100.00 | 【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【<br>100.0<br>: ﺭﺋﻴﺴﻴﺔ ﻣﻴﺰ | נסם סטורית | 100.00 | ל, ישר סטוריה | | | 100.00 - | 1000000 | |
| | | ് മാക്കു<br>ﻬ | 心之一 | 1 - DS - B | 10-14-1 | ುಗಳಿನ | ្រី<br>្រី | ి గ్రామం నుండి 10 కి.మీ. ల | ි පිහිටි විස්ත්‍රී ලංකාවේ පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි<br>' | לייני ביטור איני | :<br>. ﺗ | | ,在线<br>: | | 人彩彩<br>、<br>" | ,一 | ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・<br>్లు సం | 00 - 10 - 10 | ok oktober 2017 at | | | 0. | | |
| | ると、ミ<br>nis-calls<br>opeats<br>んと<br>Total no<br>due ta<br>ન્ડ્રેન્ડ<br>న్న | 。 参考文献 | -202 | 0 3 | 。 2017-04-06 10:40 【 | 2017 | 0-20 - 1<br>ﺮ ﺗﺮﻳﺒﻲ ﺑﻴﻨﻴﻮﻧﻴ | | . "Հ<br>المقال المقارمة المقاربة المقاومة المستوى المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب ال | | | | | , | 09:00<br>なんです | ្នុង | ్ ర | | | -10多 | | 200 - 13 - 1 | Age of | |
| | ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・<br>ested, per<br>Number of<br>Plasmids<br>mutation<br>12.255 | | | | 0 | 0 | ﺴﺎ | L | C | | | 0 | | 0 | | 0 | 0 | 0 | 0 | L | U | 0 | 0 | |
| | Number of<br>ested, per<br>mutation<br>Coll Lines<br>ﺗﻢ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟ | | | | | ﺎ | 0 | 0 | | 0 | | 0 | U | | 0 | 0 | 0 | | | 0 | 0 | ದ | 0 | |
| | nber of<br>pendent?<br>ation and<br>场 - 2017-02-04 11:42:54 来源: 2017-08-08 11:52:54 来源: 2017-08-08 11:52:54 来源: 2017-08-08 11:52:57 【字号: 2017-08-20 11:00:00 【字号: 2017-08-20 11:00 11:00 【字号: 2017-08-20 11:00 1<br>ed, per<br>moles<br>inical<br>로 불렀다. 이 글 | ひ | ਟ | ಕ್ಕೆ | | g | ల | ్ | ്ച | g | m | క | 0 | 162 | こ | S | 13 | | ਟ | 12 | 1 | ਟ | P | |
| | | G85E # | 94 del T | R17H # | Y12Z | 521+1G>T | 11+1G>T | 078del | R334W # | 2347 Pmut | 347 Hmu | A455E # | 1507 mut A | dF508mut # | V520 | 717-1G>A | G542X # | SSAAN | S549R | G551D # | 853X # | A559. | 25607 # | |
| | | | Exon 3 | |…