(251 days)
No
The description focuses on the biochemical components and the data analysis software (TDAS) for interpreting the results of the genetic assay. There is no mention of AI or ML algorithms being used for data analysis or interpretation.
No.
The device is a qualitative genotyping test used for carrier testing, newborn screening, and diagnostic testing for mutations in the CFTR gene. It aids in diagnosis but does not directly provide therapy.
Yes
The "Intended Use / Indications for Use" section states that the device provides "information intended to be used for ... confirmatory diagnostic testing in newborns and children."
No
The device description explicitly lists multiple hardware components, including PCR Primer Mix, ASPE Mix, Bead Mix, various enzymes, and buffers, in addition to the software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is used to "simultaneously detect and identify a panel of mutations and variants in the cystic fibrosis transmembrance regulator (CFTR) gene in human blood specimens." This involves testing a sample taken from the human body (in vitro) to provide information about a medical condition (diagnostic).
- Specimen Type: The device uses "human blood specimens," which are biological samples taken from the body.
- Purpose: The test provides "qualitative genotyping 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." These are all diagnostic or screening purposes related to a medical condition.
- Device Description: The components listed are typical of a molecular diagnostic assay used to analyze genetic material from a biological sample.
The definition of an In Vitro Diagnostic device is a medical device that is intended for use in vitro for the examination of specimens, including blood and tissue samples, derived from the human body, solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the safety and compatibility of transfusions, or to monitor therapeutic measures. This device clearly fits this definition.
N/A
Intended Use / Indications for 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.
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.
Product codes
NUA
Device Description
The xTAG CFTR 39 kit v2 includes the following components:
- 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
- Platinum® TFI DNA Polymerase .
- Platinum® TFI Reaction Buffer .
- TFI MgCl2 .
- Shrimp Alkaline Phosphatase .
- Exonuclease I .
- Strepavidin-Phycoerythrin Conjugate .
- xTAG Data Analysis Software (TDAS) CFTR .
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adults of reproductive age, newborns and children.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
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.
N for C cateluations = nolal number of interprodent samples tested = 319 clinical samples, 8 cell lines, and plasmids
Overall Accuracy Per Sample Before Reruns: 327/327 = 100.00%
Overall Accuracy Per Sample After Reruns: 327/327 = 100.00%
Table 1 demonstrates 100% accuracy compared with the reference method.
a) Precision/Reproducibility:
A multi-centre, multi-operator, multi-lot, blinded study design was used to evaluate total variability of the xTAG Cystic Fibrosis 39 kit.
The xTAG Cystic Fibrosis 39 kit v2 assay detected all 39 mutations, as well as normal (wild-type) alleles, with a precision of > 99.54% across 3 sites, between 6 operators (2 per site) and between reagent lots (a total of 3 lots, 1 lot per site). Sample 34 (Coriell genomic DNA) made a 'No Cal' after an allowable rerun at Site 3 (operator 1) whereas sample 37 (plasmid) made 3 miscalls at Site 1 between 2 operators.
Reproducibility of detection of a compound heterozygote dF508 / F508C was also characterized in this study. Of the 36 rest of ex 30 generated a dF508 HET call and 6 generated a dF508 Mu D call. Both results are accurate when taking into consideration the definition of a Mu call (i.e. only the mutant allele is detected).
Total number of calls (All Sites) Before Allowable Re-Run for Total WT Calls across all samples: 54612
Total No. Missed Calls: 0
Total No. No Calls: 0
Total No. Correct Calls: 54612
% Agreement with Comparator: 100.00
LB of 95% CI: 99.841
UB of 95% CI: 99.993
Total number of calls (All Sites) After Allowable Re-Run for Total WT Calls across all samples: 54612
Total No. Missed Calls: 0
Total No. No Calls: 0
Total No. Correct Calls: 54612
% Agreement with Comparator: 100.00
LB of 95% CI: 99.993
UB of 95% CI: 100.00
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Accuracy (After allowable re-run): 100.00%
Precision (between site and between operator): 100% correct calls for most samples with N=438 calls per operator per site, with some exceptions:
Sample 34 (dF508): Op1 Site 1 (N=438, 100%), Site 2 (N=438, 100%), Site 3 Op1 (N=437, 99%), Site 3 Op2 (N=438, 100%).
Sample 37 (1898+5G>T): Op1 Site 1 (N=12, 91.67%), Op2 Site 1 (N=12, 83.33%), Site 2 (N=12, 100%), Site 3 (N=12, 100%).
Reproducibility (After allowable re-run, per allele):
% Agreement with Comparator is 100.00% for most alleles (e.g., G85E, 394delTT, R117H, etc.)
dF508: (N=468) Before Re-Run % Agreement 96.58 (LB 94.51, UB 98.03), After Re-Run % Agreement 99.57 (LB 98.46, UB 99.95).
1898+1G>A: (N=36) Before Re-Run % Agreement 97.22 (LB 85.47, UB 99.93), After Re-Run % Agreement 100.00 (LB 90.26, UB 100.00).
2307insA: (N=36) Before Re-Run % Agreement 91.67 (LB 77.53, UB 98.25), After Re-Run % Agreement 91.67 (LB 77.53, UB 98.25).
Total WT Calls across all samples: (N=54612) % Agreement 100.00 (LB 99.993, UB 100.00) after allowable re-run.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.
(a)
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.(b)
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.
0
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: 416.593.4323 x374 Fax: 416.593.1001 Contact person: Gloria Lee
Proprietary and Established Names: xTAG® Cystic Fibrosis 39 kit v2
Regulatory Information:
-
Regulation Section:
21 CFR 866.5900, CFTR (cystic fibrosis transmembrane conductance regulator) gene mutation detection system -
Classification: Class 11
-
Product Code: NUA
-
Panel: lmmunology (82)
510(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.
Page 1 of 13
1
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
2
- 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
| 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 | |
| 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 | ||
| worlds most common and North American-prevalent | ||
| mutations. | The xTAG Cystic Fibrosis Kit 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 worlds | ||
| most common and North American-prevalent | ||
| mutations. | ||
| Indications | ||
| for Use | 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 xTAG Cystic Fibrosis Kit 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. | ||
| Contra- | ||
| Indications | 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. | 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. | ||
| Type of Test | Multiplex PCR followed by multiplex allele specific | |
| primer extension for genotyping, hybridized to multiplex | ||
| fluorescent microparticles, detected by flow cytometry | Multiplex PCR followed by multiplex allele | |
| specific primer extension for genotyping, | ||
| hybridized to multiplex fluorescent | ||
| microparticles, detected by flow cytometry. | ||
| Product | ||
| Description | Tests for 39 mutations and 4 variants in the CFTR gene | |
| (23 of which are recommended by ACMG/ ACOG). The | ||
| mutations and variants are the same as those tested for | ||
| by the predicate device | Tests for 39 mutations and 4 variants in the | |
| CFTR gene (23 of which are recommended by | ||
| ACMG/ ACOG). |
510(k) summary for xTAG® CFTR 39 kit v2
Luminex Molecular Diagnostics Inc.
Page 3 of 13
3
| Specimen
| Type | Peripheral human whole blood. | Peripheral human whole blood. | ||||||
|---|---|---|---|---|---|---|---|---|
| Instrument | ||||||||
| System | Luminex 100 or 200 IS | Luminex 100 or 200 IS | ||||||
| Software | TDAS CFTR contains 1 template to detect for | |||||||
| mutations. Software masking function where user can | ||||||||
| chose to display results for only the ACMG / ACOG | ||||||||
| 23 mutations or the full panel of mutations. | TDAS CF-I contains 1 template to detect for 39 | |||||||
| mutations and 4 variants. | ||||||||
| Mutations | ||||||||
| 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
4
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.
.
Page 5 of 13
.
.
5
| Extra for |
|---|
| ' kit v2 |
| 20 |
| TR 39 |
| Allers consiste accessfile and on |
| XIAG |
| 5 |
| 1 |
| 19 10 10 10 100 |
| 194 199 |
- |
| Resu |
| 1
t |
| " curacy . |
| 1 |
| ANTING |
| 0 |
| Tahl |
:
:
. 1
:
| and the second and the same of the | 5% | 6-100 | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | :行 | 1001000 | 100 | 2017 - 11:40 | 100
ស់មកព្រះគ្រឿង | ระเทศอ | 1 - 1947 - 1994
22: 110 | 100
11 285 25 | ﺍﻟﻤﺴﺎﻋﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ
100 100 | ా చియ | 100!0 | a 3
001888
123 11 | ് 100 0 | 100.00 | ים חיים מיני מ | 100.0 | ്കുന്നതിന്റെ അവലംബം എന്നും വിശ്വാസം പ്രവരിച്ചു. അവലംബം പ്രശസ്തമായി പ്രവുമാനിക്കുന്നു. അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം അവലംബം | 1882338 | | |
|------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|-----------------------------------------|---------------|
| | ci 14
01 85
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
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 %
Accuracy Accuracy Accuracy
40 3
Repear
ី | 100.00 - | 100.00 1
ర్లు ప్రసిద్ధి ప్రసిద్ధి ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ప్రాథమిక ఆరోగ్య కేంద్రం, ప్రాథమిక ఆరోగ్య కేంద్రం, ప్రాథమిక
ーディ
តែ | - 00 00 -
- 2018-7 | ้างอิง ตัวเล่
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 -
,部落 | 100.00
ישורים יום יותר | 12.00
ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺎ | 100 000
新闻网 | מחמש מ
的一个 | ្រី | 100.00
13 - 10 - 10 -
,一直一直 | 1984 1999
100 80 | 人 最新 | 00
ម្រាប់ប្រជាជាបា
EUTFB | 100.00
0 0 4 1 | 1100000
2017-09-09 11:40:00 | 100 ตุลา อ
100 000
,在线 | 100.00 -
לייני מיני מיני או | 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000
STIDENDERS
: 上一 | 100.00 1
ransar ke | 100.00
2017 | ้า - 10 - 100.00 - | 180:00
်ရေးနှင့် မြို့နယ်ရှိ ရွာများ | |
| | Total no al Total no al Tre
មានក្រុមព្រំ ថា កំណត់ ១០គែល ១០គែល | 发行业
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
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 :
: | 100.00 | 20100.00 | 100.00 | יינו | 100000 | 10000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | : 100.00 - 1 | 100:00 | ,这
100:00
.
なる。 | ల్లా రాజార్లు
100:0 | 100.00 1 | 100.00 | 【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【 】【
100.0
: ﺭﺋﻴﺴﻴﺔ ﻣﻴﺰ | נסם סטורית | 100.00 | ל, ישר סטוריה | | | 100.00 - | 1000000 | |
| | | ് മാക്കു
ﻬ | 心之一 | 1 - DS - B | 10-14-1 | ುಗಳಿನ | ្រី
្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
' | לייני ביטור איני | :
. ﺗ | | ,在线
: | | 人彩彩
、
" | ,一 | ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
్లు సం | 00 - 10 - 10 | ok oktober 2017 at | | | 0. | | |
| | ると、ミ
nis-calls
opeats
んと
Total no
due ta
ન્ડ્રેન્ડ
న్న | 。 参考文献 | -202 | 0 3 | 。 2017-04-06 10:40 【 | 2017 | 0-20 - 1
ﺮ ﺗﺮﻳﺒﻲ ﺑﻴﻨﻴﻮﻧﻴ | | . "Հ
المقال المقارمة المقاربة المقاومة المستوى المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب المنتخب ال | | | | | , | 09:00
なんです | ្នុង | ్ ర | | | -10多 | | 200 - 13 - 1 | Age of | |
| | ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
ested, per
Number of
Plasmids
mutation
12.255 | | | | 0 | 0 | ﺴﺎ | L | C | | | 0 | | 0 | | 0 | 0 | 0 | 0 | L | U | 0 | 0 | |
| | Number of
ested, per
mutation
Coll Lines
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
pendent?
ation and
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
ed, per
moles
inical
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 | | | Exon 4 | Exon 5 | | | | Exon 7 | EXON 9 | | | Exon 10 | | | | | | | | EXON 11 | |
| | And Control Concession of the Comments of | | ್ತಿ ಸ್ವರ್ | 0000000000 | 100000 | | | 100 00 | 00 00 | 00 00 | | ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘ | 100 0 | 100:00 | ్లాల్లో వ | | | 100.00 | | 21839 | | | | |
| 发电影 | | -15:81 | 15:81 1 | - 15.61. | 2 50 1 | ﺍﻟﻤﻮﺿﻮﻉ: 24 ﻣﺮﺓ : ﺍﻟﻤﺴﺘﻘﻠﺔ : ﺍﻟﻤﺘﻮﻗﻒ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴﺘﻮﻯ : ﺍﻟﻤﺴ | 17:47:82 14 | 159 04 2 | 8
ਸ਼ਾ | 1 15 81 2 | | 100 00 - 1 - 47 82 - | 100.00 1 39.76 | :
39.75 | 75:29
1000 | - 39.76 | 29:24 - | - 15.81 | Sales C | 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 1999 1999 1999 1999 1999 1999 1999 1999 1999 1999 | 47.82 | 47.62 | ి 250 హ | |
| 行可能量的 | curag
epea
taffe | 100 ﻣﻦ 1 | | 1 100 0 | 发
,在线 | 100 00 1 | 100.00 1
Rest Marine | - 100.00 | 9 100.00 | | 100.00 11:15 81 | | | 100 DO | の一般的な | 2008 | Al Other
ﺍﻟﻤ | 100.00 בסוג | 100:00 | 23100.00 188 | 4-100.00 - | 100.00 - | -100 00 | |
| After allowable re-run | no
repeab due 10 mi calls
atal
的 | , | 10000 | ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘ | a o ar | ົວລາວ ວັນທຸກ | ﺍﻟﻤﺴﺎﻋﺪﺓ ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ | 10 - 1
್ಕಾರ | 10
335 | : * n - | 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | ນ ການປະຕິທິນ | ,可是 | - 30 - 游 | 02
ﺍﻟﻤﺴﺎﻋﺪﺓ | 100 | 新闻 09:5 | 100000 | -08-07-08 | 2012 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 | 2-08-08-23 | ిల్లో గ్రామం నుండి | : 2017-02-09 1 | 10 0 10 |
| | otal no. epents due lo
્યત્વે તે
cal
న్నారు. సమీప ప్రాథమిక ప్రస్తుంది. సం
S | ﻟﻤﺘﺤﺪﺓ ﺍ | a sobre | | 的电子 | ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ
16
网 | ka olem | ﻋﻴﻦ 0 ﺷﻬﺪ | יים מיני
12.0 | 动力的 | ,一个一 | : 0 - 0 - 2 | 2007 20 | 1 - 10 - 10 - 15 | | ,你
, | | 2017 | 0-20-201 | | 发 - 0- 8- | : 0 游 | 1 2017 | 10 0 1 |
| .
| B of 95
(
1 | 100.00 - 1 | 100.00 | -100.00
، ﻳﺴﺘﺨﺪﻡ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴ
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | 100.00 | | 100.00 - 100.00 - | 100.00 - | 100:00 - | 100.00 1 | 100.00 | 00.00 2
****************************************************************************************************************************************************************************** | 00:00 00
ﻢ | 100:00 00 % | المواقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع المو | SERTAL PRODUCT PRODUCT CARTER CONSTITUTION CONTRACT CARACT CARACT CARACT CARACT CARACT CARALAR CASTER CASTER CASTER CASTER CASTER CASTER CASTER CASTER CASTER CASTER CASTER CA
CO | 100 | Proved Contraction
00:00:00 | 100:00 - | 100:00 # | : 100.00 | #100.00 # | 100.00 # | 00 000,00 |
| ్రాలు సంరక్షణ కా
. ﻟ | Librof 95%
No
Timb
្ញុំ
イ | | й хүвтэй | ﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤ
1581
, | 12:50 A | 29:24 | 147.82 | 59.04
: | 15 81 | 277
215.81-2 | 1581 | 47.82 | 39.76 | 39:76:13 | 11:11:11 75:29:13 | 39.76 | 29 | 15 81 - 3
r | 63.06 3 | 54.074. | 2 47 82 8 | 47:82 % | 2.50 . 2.50 | 47.82 - 47.82 |
| | repeats C
ിലെ വേണ്ടും അവലംബം പ്രാവുന്നും പുറത്തിനും പുറത്തിനും പ്രാ | 100.00 00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | 100.00 | 100.00 | 100.00 | יינו מס סם מסוי | 100.00 2018 | ్ట్స్ ప్ర
100.00 | ,
100,00 | 100.00 00 | 100.00 | 人 | 100.00 | 100.00 3 | ้านี้ | ์ 100 ออ | ﺗﻔ
100 | 100.00 | 100.00 | 00-00-100 | 100.00 | 100.00 | 100.00 | 100 00 00 100 |
| Before Allowable re-run | due to no
Total no. of repeats due to no
ﮯ " | បើក្រោយប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រើប្រ
| 新闻娱乐 | | ,管理委员 | 2008 32 | 费 of ex | September | יי מסגרי ל | 11:00 15 | | 2007-00-00 | : 新闻: 大
: 大 : 大 : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : | 100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | | | 2002 | 2013
ಷ್ಟ | 第一次回 教授 | ಿ ಸಾಮಾರ್ಯ ಸ | 200% | 2008 200 | 202020 | 新闻网 2019-09-2 |
| | Number of Total no.
dia calle Listaille City of Callege
ప్ర
epeats | | ್ --------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | , | 0 - 4- | o " | క్కడ వైద్యశాల | 6711
0- | | 1 - 1 - 1 - 1 | 00: (^ 2
1 3.6 % | | 0 - - | : | | 0 2 2 | 第一次会 | 10 201 | 20192 | 18 | | | |
| | lasmids :
ested, pe
nutation
ರ | 0 | C | U | 0 | 0 | 0 | 0 | ਟ | 0 | 0 | 0 | 0 | | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | | 0 |
| | mutation s
mber o
II Lines
, pe
60 | U | 0 | J | ﺎ | 0 | D | 0 | D | D | C | | 0 | l | 0 | ﺎ | | 0 | 0 | 0 | 0 | 0 | | 0 |
| | er of
d, per. Nion ma
pendent
inica
อน | | 0 | | | ్ | S | 1 | 0 | ਟੈ | 0 | 4 | | ਸ | € 1 | ਬ | ﺎ | ਟ | | లు అ | క్ | ਪ੍ਰ | 0 | ಳು |
| | | 890 • 1 G > A | 898+5G> | 2183AA>C | 184 del A | 2307 insk | 789+5G>A | 3120+1G>/ | 1092X-C> | 1092X-C> | M1101K | R1162X # | 26599910 | | 849+10kb | S1255X20 | 3876dell | | 3905insT W1203K # | | 606V-var tg | 06V-varia | 607V-variar | 508C-varian |
| | | | Exon 12 | | | Exon 13 | EXON 14 | Exon 16 | | | Exon 17 | | | Exon 19 | NTRON 19 | | | | EXON 2 | | EXON TO | | | |
.
.
:
.
·
,一
, ·
:
:
,
510(k) summary for xTAG® CFTR 39 kit v2
Luminex Molecular Diagnostics Inc.
,
.
Page 6 of 13
f 13
,
:
6
Table I (continued). Summary of Accuracy Study Results for the xTAG CFTR 39 kit v2
- 1 - 1
.
510(k) summary for xTAG® CFTR 39 kit v2
Luminex Molecular Diagnostics Inc.
:
:
. . .
:
Page 7 of 13
:
7
| Basis for Overall
Exon or Intron Accuracy
Calculation | Number of
Independent
Clinical Samples
Tested | Number of
Cell Lines
Tested | Number of
Plasmids
Tested | Number of
Reruns | Overall Accuracy
Per Sample
Before
Reruns | LB of 95% CI
(before
reruns) | UB of 95% CI
(before
reruns) | Overall Accuracy
Per Sample
After
Reruns | LB of 95% CI
(after
reruns) | UB of 95% CI
(after
reruns) |
|-------------------------------------------------------------|--------------------------------------------------------|-----------------------------------|---------------------------------|---------------------|----------------------------------------------------|------------------------------------|------------------------------------|---------------------------------------------------|-----------------------------------|-----------------------------------|
| Overall accuracy
per sample.
all exons | 319 | 8 | not used in
calculation | 0 | $327/327 =100.00$ | 98.88% | 100.00% | $327/327 =100.00$ | 98.88% | 100.00% |
- It is critical to include all relevant independent variables in the model.
- Omitted variable bias occurs when a relevant independent variable is omitted from the model.
- The error term includes the effects of all factors, known and unknown, that determine the value of the dependent variable, other than the independent variables included in the model.
- Total Sum of Squares (SST) = Explained Sum of Squares (SSE) + Sum of Squared Errors (SSR)
- R2 = SSE/SST = 1 - SSR/SST
- Adjusted R2 always less than or equal to R2
- Multicollinearity exists when two or more independent variables are highly correlated.
- N for C cateluations = nolal number of interprodent samples tested
1 U = Upper Bound, LB = Lower Bound Cl = Confiente interval. Cloper-Pearson Cl calculator provided by Jo
able 1 demonstrates 100% accuracy compared with the reference meth
Analytical Performance Characteristics
a) Precision/Reproducibility:
PRECISION REPRODUCIBILITY
multi-centre, multi-operator, multi-lot, blinded study design was used to evaluate total variability of the xTAG Cystic Fibrosis 39 kit
The renocitive in anytol (o 11 has 10 carea in Chicfich Marial Concertal Concercial Concercial Concercuit Concercuit Concercuitorial concerner commender commender commendo po
510(k) summary for xTAG® CFTR 39 l
Luminex Molecular Diagnostics Inc.
Page 8 of 13
8
.
. .
:
:
:
Table 2, Reproducibility for xTAG Cystic Fibrosis 39 kit v2 (between site and between operator)
| Operator - to - Operator | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Site 1 | Site 2 | Site 3 | ||||||||||||
| Sample | Genotype | Op 1 | ||||||||||||
| N | Op 1 | |||||||||||||
| % corr | Op2 | |||||||||||||
| N | Op2 | |||||||||||||
| % corr | Op1 | |||||||||||||
| N | Op1 | |||||||||||||
| % corr | Op2 | |||||||||||||
| N | Op2 | |||||||||||||
| % corr | Op1 | |||||||||||||
| N | Op1 | |||||||||||||
| % corr | Op2 | |||||||||||||
| N | Op2 | |||||||||||||
| % corr | ||||||||||||||
| 1 | 711+1G>T | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 2 | 1717-1G>A | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 3 | G542X | R117H | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 4 | A455E | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 5 | 3659delC | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 6 | R1162X | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 7 | 3849+10kbC>T | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 8 | W1282X | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 9 | 1078delT | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 10 | A559T | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 11 | S549N | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 12 | G551D | R347P | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 13 | 3905insT | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 14 | R560T | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 15 | 394delTT | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 16 | R553X | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 17 | 2184delA | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 18 | 1898+1G>A | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 19 | Y1092X-C>A | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 20 | 2183AA>G | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | |
| 21 | V520F | 3120+1G>A | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
510(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.
ﺋﯩﻦ
.
・・・
.
. : . . .
: . : Page 9 of 13 . 、
. .
:
9
| Sample | Genotype | Site 1 | Site 2 | Site 3 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Op 1 | |||||||||||||
| N | Op 1 | ||||||||||||
| % corr | Op2 | ||||||||||||
| N | Op2 | ||||||||||||
| % corr | Op1 | ||||||||||||
| N | Op1 | ||||||||||||
| % corr | Op2 | ||||||||||||
| N | Op2 | ||||||||||||
| % corr | Op1 | ||||||||||||
| N | Op1 | ||||||||||||
| % corr | Op2 | ||||||||||||
| N | Op2 | ||||||||||||
| % corr | |||||||||||||
| 22 | R334W | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 23 | 2789+5G>A | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 24 | 612+1 G>A | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 25 | d1507 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 26 | dF508 (+ | ||||||||||||
| F508C variant) | 439* | 100 | 442** | 100 | 438*** | 100 | 438*** | 100 | 439* | 100 | 438*** | 100 | |
| 27 | G85E | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 28 | N1303K | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 29 | M1101K | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 30 | Y122X | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 31 | R347H | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 32 | 3876delA | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 33 | S549R | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 |
| 34 | dF508 | 438 | 100 | 438 | 100 | 438 | 100 | 438 | 100 | 437 | 99 | 438 | 100 |
| 35 | dF508 | ||||||||||||
| (+1506V variant) | 18 | 100 | 18 | 100 | 18 | 100 | 18 | 100 | 18 | 100 | 18 | 100 | |
| 36 | V520F | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 |
| 37 | 1898+5G>T | 12 | 91.67 | 12 | 83.33 | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 |
| 38 | 2307insA | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 |
| 39 | 3791delC | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 |
| 40 | Y1092X-C>G | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 | 6 | 100 |
| 41 | S1255X (ex.19) | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 | 12 | 100 |
| 42 | S1255X (ex.20) |
Tuble 2 (continued). Reproducibility for xTAG Cystic Fibrosis 39 kit v2 (between site and between operator)
- Site 1 = Hartford Hospital; Connecticut. USA; Site 2 = Luminer Molecular Diagnostics, Toronto, Canada; Site 3 = Hospital for Sick Children, Toronto, Canada.
† Op = operator (1 or 2)
** N, number of calls
+, % corr, percent correct
t, % correct correct
- Total Number of calls 438 + 1 = 439, because TDAS mude one dF508 Mu D call (F508C varian was unmaked)
Total Number of calls 438 + 4 = 442, because TDAS made 4 dF508 Mu D calls ( F508C variant was unmasked)
Total Number of calls = 438, because TDAS made all dF508 HET calls (F508C variant was masked)
Tatle 2 shows that the xTAG Cystic Fibrosis 39 kit v2 assuy detected all 39 mutations, as well as normal (wild-type) alleles, with a precision of > 99,54% across 3 sites, between 6 operators (2 per site) and between reagent lots (a total of 3 lots, 1 lot per site). Sample 34 (Coriell genomic DNA) made a 'No Cal' after an allowable rerun at Site 3 (operator 1) whereas sample 37 (plasmid) made 3 miscalls at Site 1 between 2 operators.
Repoducibility of detection of a compound heterozygote dF508 / F508C was also characterized in this study. Of the 36 rest of ex 30 generated a dF508 HET call and 6 generated a dF508 Mu D call. Both results are accurate when taking into consideration the definition of a Mu call (i.e. only the mutant allele is detected).
S10(k) summary for xTAG® CFTR 39 kit v2 Luminex Molecular Diagnostics Inc.
Page 10 of 13
10
Table 3 Reproducibility of the xTAG Cystic Fibrosis 39 kit v2 (per allele) ;
・・・
| Over All 3 Sites | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Before Allowable Re-Run | After Allowable Re-Run | |||||||||||||||
| Panel | Genotype | Total # calls | ||||||||||||||
| (All Sites) | Total No. | |||||||||||||||
| Missed Calls | Total No. | |||||||||||||||
| No Calls | Total No. | |||||||||||||||
| Correct Calls | % Agreement | |||||||||||||||
| with | ||||||||||||||||
| Comparator | LB of | |||||||||||||||
| 95% | ||||||||||||||||
| CI * | UB of | |||||||||||||||
| 95% | ||||||||||||||||
| CI * | Total No. | |||||||||||||||
| Missed Calls | Total No. | |||||||||||||||
| No Calls | Total No. | |||||||||||||||
| Correct Calls | % Agreement | |||||||||||||||
| with | ||||||||||||||||
| Comparator | LB of | |||||||||||||||
| 95% | ||||||||||||||||
| CI * | UB of | |||||||||||||||
| 95% | ||||||||||||||||
| CI * | ||||||||||||||||
| A | G85E | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 394delTT | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R117H | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | Y122X | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 621+1G>T | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 711+1G>T | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 1078delT | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R334W | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R347P | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R347H | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | A455E | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | dI507 | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | dF508 | 468 | 0 | 16 | 452 | 96.58 | 94.51 | 98.03 | 0 | 2 | 466 | 99.57 | 98.46 | 99.95 | ||
| A | V520F | 72 | 0 | 0 | 72 | 100.00 | 95.01 | 100.00 | 0 | 0 | 72 | 100.00 | 95.01 | 100.00 | ||
| A | 1717-1G>A | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | G542X | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | S549N | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | S549R | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | G551D | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R553X | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | A559T | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | R560T | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 1898+1G>A | 36 | 0 | 1 | 35 | 97.22 | 85.47 | 99.93 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 1898+5G>T | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 2183AA>G | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 2184delA | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | ||
| A | 2307insA | 36 | 0 | 3 | 33 | 91.67 | 77.53 | 98.25 | 3 | 0 | 33 | 91.67 | 77.53 | 98.25 |
510(k) summary for xTAG® CFTR 39 kit v2
Luminex Molecular Diagnostics Inc.
Page 11 of 13
11
| A | 2789+5G>A | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A | 3120+1G>A | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | Y1092X-C>G | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | Y1092X-C>A | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | M1101K | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | R1162X | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | 3659delC | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | S1255X(19) | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | S1255X(20) | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | 3849+10kb | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | 3876delA | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | 3905insT | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | W1282X | 72 | 0 | 0 | 72 | 100.00 | 73.54 | 100.00 | 0 | 0 | 72 | 100.00 | 73.54 | 100.00 |
| A | N1303K | 36 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 | 0 | 0 | 36 | 100.00 | 90.26 | 100.00 |
| A | Total WT Calls | |||||||||||||
| across all samples | 54612 | 0 | 0 | 54612 | 100.00 | 99.841 | 99.993 | 0 | 0 | 54612 | 100.00 | 99.993 | 100.00 |
JB = Upper Bound, LB = Lower Bound, Cl = Confidence Interval. Exact calculation (Clopper & Pearson (1934) Biometrika 26, 404-143.) Excel Macro fro http://statpages.org/confing.htm
The TC C Cyst Fibrois 3 V ir vasar ( vild-type liles of to ssayd with repodcility (atra lows roms of 0.7%.
(fo alle 230%, 9.5% dele drobe in erminine alles brune, mines all a after allowable re-runs
Traceability, Stability, Expected Values (controls, calibrators, or method N/A
o Decembra ara e of anya o mana in tota e a manual a 10 aliento anaraman a 30, an. 2. 2. a.
Sami C. 24 and or manimal in Armanian 200 and 2004 and 2001 and 2000 and 2000 and
Inalytical Specificity | Interfering Sub stance
610(k) summary for xTAG® CFTR 39 kit
Luminex Molecular Diagnostics Inc.
Page 12 of 13
12
A hinteries sur was online the dieser of new in the sepect o to team in who thou amber (200 w/m.
Immering 20 w/n. birtered minerer wer sersein in o opervling operial on bindi
e) Stability:
The expiration date for xTAG CFTR 39 kit v2 will be based on real-time stability testin
f) Assay Cut-off
N/A
.
510(k) summary for xTAG® CFTR 39 I
Luminex Molecular Diagnostics Inc.
xTAG® CFTR 39 Kit
Summary for
Luminex Molecular Diagnostics Inc.
13
Image /page/13/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping human figures or abstract shapes, creating a sense of unity and connection.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002
Luminex Molecular Diagnostics, Inc. c/o Gloria Lee 439 University Avenue, Suite 2000 Toronto. Ontario Canada M5G 1 Y8
SEP - 1 2009
Re: K083846
Trade/Device Name: xTAGTM Cystic Fibrosis 39 Kit v2
Regulation Number: 21 CFR 866.5900
Regulation name: CFTR (cystic fibrosis transmembrane conductance regulator) gene mutation detection system
Regulatory Class: Class II Product Code: NUA Dated: August 24, 2009 Received: August 25, 2009
Dear Ms. Lee:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must
14
Page 2 - Luminex Molecular Diagnostics, Inc.
comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours,
Reena Philip
10 Y
Maria M. Chan, Ph.D. Director
Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
15
Indications for Use
510(k) Number: K083846
xTAG® Cystic Fibrosis 39 kit v2 Device Name:
Indications For 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.
X Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Alewa Philip
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K083846
Page 1 of 1