Draft Genetic Test Review
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Cystic Fibrosis
Clinical Validity
(436KB)
CLINICAL VALIDITY
Question 18: How often is the test positive when the disorder is present?
Question 19: How often is the test negative when the disorder is not present?
Question 20: Are there methods to resolve clinical false positive results in a timely manner?
Question 21: What is the prevalence of the disorder in this setting?
Question 22: Has the test been adequately validated on all populations to which it may be offered?
Question 23: What are the positive and negative predictive values?
Question 24: What are the genotype/phenotype relationships?
Question 25: What are the genetic, environmental or other modifiers?
CLINICAL VALIDITY
Question 18: How often is the test positive when the disorder is present?
Question 19: How often is the test negative when the disorder is not present?
page 1 | page 2 | page 3 | page 4
Appendix C. Published Mutation Frequency Data Derived from the Cystic Fibrosis Genetic Analysis Consortium Data for Hispanic Caucasians
Table 3-16 contains a re-analysis of the Cystic Fibrosis Genetic Analysis Consortium Data for Hispanic Caucasians (Kazazian, 1994). The study sites are listed in the same order as in the original publication. The cystic fibrosis mutations are also arranged as published. Three mutations are included in this table that are not part of the recommended prenatal panel, and three other mutations are not available in that publication that are part of the panel. The table spans two pages.
Table 3-16. Reanalysis of Mutation Frequencies from the Cystic Fibrosis Genetic Analysis Consortium Data
| USA, CO |
129 |
|
0 |
0 |
|
|
2 |
|
|
| USA, NY |
49 |
|
0 |
0 |
|
|
2 |
|
|
| USA, TX |
12 |
|
|
|
|
|
|
|
|
| USA, IL |
10 |
|
|
0 |
|
|
|
|
|
| Mexico |
160 |
|
|
|
|
|
|
|
|
| Brazil |
500 |
|
|
|
|
|
|
|
|
| Argentina |
98 |
|
|
|
|
|
|
|
|
| Total |
958 |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
0 |
| Uncorrect Rate |
|
0.00% |
0.00% |
0.00% |
0.00% |
0.00% |
0.42% |
0.00% |
0.00% |
| Chromosome Denominator |
|
0 |
178 |
188 |
0 |
0 |
178 |
0 |
0 |
| Correct Rate |
|
|
0.00% |
0.00% |
|
|
2.25% |
|
0.00% |
Table 3-16 (cont.)
| USA, CO |
129 |
0 |
59 |
0 |
7 |
|
0 |
1 |
|
| USA, NY |
49 |
0 |
22 |
0 |
2 |
0 |
2 |
0 |
0 |
| USA, TX |
12 |
|
10 |
|
0 |
|
0 |
0 |
|
| USA, IL |
10 |
|
3 |
|
2 |
0 |
0 |
0 |
|
| Mexico |
160 |
2 |
48 |
|
10 |
1 |
0 |
1 |
|
| Brazil |
500 |
|
235 |
|
28 |
|
1 |
4 |
0 |
| Argentina |
98 |
|
59 |
|
0 |
|
0 |
0 |
|
| Total |
958 |
2 |
436 |
0 |
49 |
1 |
3 |
6 |
0 |
| Uncorrect Rate |
|
0.21% |
45.51% |
0.00% |
5.11% |
0.10% |
0.31% |
0.63% |
0.00% |
| Chromosome Denominator |
|
338 |
958 |
178 |
958 |
219 |
958 |
958 |
549 |
| Correct Rate |
|
0.59% |
45.51% |
0.00% |
5.11% |
0.46% |
0.31% |
0.63% |
0.00% |
Table 3-16 (cont.)
| USA, CO |
129 |
|
|
|
2 |
|
3 |
1 |
0 |
| USA, NY |
49 |
|
|
|
0 |
|
0 |
0 |
3 |
| USA, TX |
12 |
|
|
|
|
|
|
|
|
| USA, IL |
10 |
|
|
|
0 |
|
0 |
0 |
0 |
| Mexico |
160 |
|
|
|
0 |
|
|
|
0 |
| Brazil |
500 |
|
|
|
|
|
|
|
11 |
| Argentina |
98 |
|
|
|
|
|
|
|
|
| Total |
958 |
0 |
0 |
0 |
2 |
0 |
3 |
1 |
14 |
| Uncorrect Rate |
|
0.00% |
0.00% |
0.00% |
0.21% |
0.00% |
0.31% |
0.10% |
1.46% |
| Chromosome Denominator |
|
0 |
0 |
0 |
348 |
0 |
188 |
188 |
848 |
| Correct Rate |
|
|
|
|
0.57% |
|
1.60% |
0.53% |
1.65% |
Appendix D. Published Mutation Frequency Data Derived from the Cystic Fibrosis Genetic Analysis Consortium Data for African Americans
Table 3-17 contains a re-analysis of the Cystic Fibrosis Genetic Analysis Consortium Data for African Americans (Kazazian, 1994). The study sites are listed in the same order as in the original publication. The cystic fibrosis mutations are also arranged as published. Three mutations are included in this table that are not part of the recommended prenatal panel, and three other mutations are not available in that publication that are part of the panel. The table spans two pages.
Table 3-17. Reanalysis of Mutation Frequencies from the Cystic Fibrosis Genetic Analysis Consortium Data
| USA, MD |
79 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
| USA, NC |
33 |
|
0 |
0 |
|
|
1 |
0 |
|
| USA, IL |
32 |
|
|
1 |
|
|
|
|
|
| USA, NY |
25 |
|
0 |
1 |
|
|
0 |
|
|
| Total |
169 |
0 |
0 |
2 |
0 |
0 |
1 |
0 |
0 |
| Uncorrect Rate |
|
0.00% |
0.00% |
1.18% |
0.00% |
0.00% |
0.59% |
0.00% |
0.00% |
| Chromosome Denominator |
|
79 |
137 |
169 |
79 |
79 |
137 |
112 |
79 |
| Correct Rate |
|
0.00% |
0.00% |
1.18% |
0.00% |
0.00% |
0.73% |
0.00% |
0.00% |
Table 3-17 (cont.)
| USA, MD |
79 |
0 |
30 |
0 |
1 |
1 |
0 |
3 |
0 |
| USA, NC |
33 |
1 |
14 |
1 |
0 |
0 |
0 |
0 |
0 |
| USA, IL |
32 |
|
8 |
|
1 |
0 |
1 |
1 |
|
| USA, NY |
25 |
0 |
8 |
0 |
0 |
0 |
0 |
0 |
0 |
| Total |
169 |
1 |
60 |
1 |
2 |
1 |
1 |
4 |
0 |
| Uncorrect Rate |
|
0.59% |
35.50% |
0.59% |
1.18% |
0.59% |
0.59% |
2.37% |
0.00% |
| Chromosome Denominator |
|
137 |
169 |
137 |
169 |
169 |
169 |
169 |
137 |
| Correct Rate |
|
0.73% |
35.50% |
0.73% |
1.18% |
0.59% |
0.59% |
2.37% |
0.00% |
Table 3-17 (cont.)
| USA, MD |
129 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
| USA, NC |
49 |
|
|
0 |
|
0 |
0 |
0 |
0 |
| USA, IL |
12 |
|
|
|
1 |
|
0 |
0 |
0 |
| USA, NY |
10 |
|
|
|
0 |
|
0 |
0 |
0 |
| Total |
169 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
| Uncorrect Rate |
|
0.00% |
0.00% |
0.00% |
0.59% |
0.00% |
0.00% |
0.00% |
0.00% |
| Chromosome Denominator |
|
79 |
79 |
112 |
136 |
112 |
169 |
169 |
169 |
| Correct Rate |
|
0.00% |
0.00% |
0.00% |
0.74% |
0.00% |
0.00% |
0.00% |
0.00% |
The mutation frequency for 3120+1G>T was reported in Table 3-3 as being found on 14 of 112 chromosome examined (Studies from NC and MD).
Appendix E. Published Mutation Frequency Data Derived from the Cystic Fibrosis Genetic Analysis Consortium Data for Ashkenazi Jewish
Table 3-18 contains a re-analysis of the Cystic Fibrosis Genetic Analysis Consortium Data for Ashkenazi Jewish (Kazazian, 1994). The study sites are listed in the same order as in the original publication. The cystic fibrosis mutations are also arranged as published. Three mutations are included in this table that are not part of the recommended prenatal panel, and three other mutations are not available in that publication that are part of the panel. The table spans two pages.
Table 3-18. Reanalysis of Mutation Frequencies from the Cystic Fibrosis Genetic Analysis Consortium Data
| USA, NY |
156 |
|
0 |
0 |
|
|
0 |
|
|
| USA,TX |
57 |
|
0 |
0 |
|
0 |
0 |
0 |
0 |
| USA, NY |
38 |
|
|
0 |
|
|
|
|
|
| USA, IL |
14 |
|
|
|
|
|
|
|
|
| Israel (Ash) |
238 |
0 |
0 |
|
|
|
|
|
|
| Total |
503 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
| Uncorrect Rate |
|
0.00% |
0.00% |
0.00% |
0.00% |
0.00% |
0.00% |
0.00% |
0.00% |
| Chromosome Denominator |
|
238 |
451 |
213 |
0 |
57 |
213 |
57 |
57 |
| Correct Rate |
|
0.00% |
0.00% |
0.00% |
0% |
0.00% |
0.00% |
0.00% |
0.00% |
Table 3-18 (cont.)
| USA, NY |
156 |
0 |
59 |
1 |
8 |
0 |
1 |
1 |
0 |
| USA, TX |
57 |
0 |
15 |
0 |
3 |
|
0 |
0 |
0 |
| USA, NY |
38 |
|
15 |
|
5 |
|
|
|
|
| USA, IL |
14 |
|
5 |
|
1 |
0 |
0 |
0 |
|
| Israel (Ash) |
238 |
0 |
64 |
2 |
21 |
0 |
0 |
0 |
0 |
| Total |
503 |
0 |
158 |
3 |
38 |
0 |
1 |
1 |
0 |
| Uncorrect Rate |
|
0.00% |
31.41% |
0.60% |
7.55% |
0.00% |
0.20% |
0.20% |
0.00% |
| Chromosome Denominator |
|
451 |
503 |
451 |
503 |
408 |
465 |
465 |
451 |
| Correct Rate |
|
0.00% |
31.41% |
0.67% |
7.55% |
0% |
0.22% |
0.22% |
0.00% |
Table 3-18 (cont.)
| USA, NY |
156 |
|
|
|
0 |
|
7 |
62 |
3 |
| USA, TX |
57 |
|
|
|
0 |
0 |
0 |
34 |
1 |
| USA, NY |
38 |
|
|
|
|
|
1 |
16 |
1 |
| USA, IL |
14 |
|
|
|
0 |
|
1 |
3 |
0 |
| Israel (Ash) |
238 |
|
|
|
|
|
15 |
116 |
9 |
| Total |
503 |
0 |
0 |
0 |
0 |
0 |
24 |
231 |
14 |
| Uncorrect Rate |
|
0.00% |
0.00% |
0.00% |
0.59% |
0.00% |
4.77% |
45.92% |
2.78% |
| Chromosome Denominator |
|
0 |
0 |
0 |
227 |
57 |
503 |
503 |
503 |
| Correct Rate |
|
0% |
0% |
0% |
0.00% |
0.00% |
4.77% |
45.92% |
2.78% |
|