| |
Draft Genetic Test Review
“This information is distributed solely for the purpose of pre dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the Centers for Disease Control and Prevention. It does not represent and should not be construed to represent any agency determination or policy.”
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 A. Published Mutation Frequency Data Derived from the Cystic Fibrosis Genetic Analysis Consortium Data for non-Hispanic Caucasians in North America
Table 3-14 contains a reanalysis of the Cystic Fibrosis Genetic Analysis Consortium Data for non-Hispanic Caucasians (Kazazian, 1994). For easy reference, the study sites are listed in the same order as in that publication. Some studies have been reclassified to satisfy the aim of limiting the analysis to studies of non-Hispanic Caucasians. The 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 present that are part of the panel. The table spans three pages.
Table 3-14. Reanalysis of Mutation Frequencies from the CF Genetic Analysis Consortium
| CAN, Toro |
1034 |
7 |
13 |
18 |
5 |
1 |
4 |
1 |
4 |
| CAN, Que |
444 |
2 |
|
57 |
13 |
|
|
|
18 |
| CAN, Que |
66 |
0 |
0 |
9 |
2 |
|
0 |
0 |
0 |
| USA, IG |
1117 |
2 |
10 |
12 |
|
0 |
0 |
6 |
0 |
| USA, NC |
1083 |
4 |
15 |
12 |
|
|
0 |
8 |
1 |
| USA, MN |
789 |
|
|
|
|
|
|
|
|
| USA, CO |
600 |
|
3 |
9 |
|
|
|
|
|
| USA, MD |
468 |
|
6 |
5 |
0 |
0 |
1 |
1 |
1 |
| USA, TX |
441 |
|
3 |
6 |
0 |
0 |
0 |
1 |
1 |
| USA, NB |
374 |
|
1 |
2 |
|
|
1 |
3 |
|
| USA, MI |
344 |
|
1 |
|
|
|
|
5 |
|
| USA, MA |
319 |
|
2 |
2 |
|
|
|
|
|
| USA, NY |
319 |
|
1 |
2 |
|
|
1 |
|
|
| USA, IL |
310 |
|
|
2 |
|
|
|
|
|
| USA, MA |
270 |
|
2 |
4 |
|
|
|
|
|
| USA, PA |
225 |
1 |
0 |
7 |
|
|
|
0 |
|
| USA, MI |
216 |
|
|
|
|
|
|
|
|
| USA, MN |
206 |
|
|
0 |
|
|
|
|
|
| USA, WA |
194 |
|
|
|
|
|
|
|
|
| USA, PA |
189 |
0 |
2 |
2 |
0 |
0 |
0 |
0 |
0 |
| USA, MA |
177 |
|
|
3 |
|
|
|
|
|
| USA, MD |
142 |
|
1 |
|
|
|
|
1 |
|
| USA, NY |
133 |
|
0 |
0 |
|
|
0 |
|
|
| USA, TX |
130 |
|
|
|
|
|
|
|
|
| USA, NY |
82 |
|
1 |
0 |
|
|
|
0 |
0 |
| USA, LA |
56 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
| USA, CA |
34 |
|
|
|
|
|
|
|
|
| USA, MA |
30 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
| Total |
9792 |
16 |
61 |
152 |
21 |
1 |
7 |
26 |
27 |
| Uncorrect Rate |
|
0.16% |
0.62% |
1.55% |
0.21% |
0.01% |
0.07% |
0.27% |
0.28% |
| Chromosome Denominator |
|
4244 |
7292 |
7943 |
2728 |
3335 |
5310 |
5651 |
5010 |
| Correct Rate |
|
0.38% |
0.84% |
1.91% |
0.77% |
0.03% |
0.13% |
0.46% |
0.54% |
Table 3-14. Reanalysis of Mutation Frequencies from the Cystic Fibrosis Genetic Analysis Consortium Data (Kazazian, 1994) - Continued
| CAN, Toro |
1034 |
7 |
725 |
5 |
25 |
0 |
30 |
4 |
8 |
| CAN, Que |
444 |
1 |
300 |
|
2 |
|
1 |
|
|
| CAN, Que |
66 |
0 |
47 |
0 |
0 |
0 |
0 |
0 |
0 |
| USA, IG |
1117 |
2 |
832 |
6 |
23 |
1 |
26 |
13 |
2 |
| USA, NC |
1083 |
3 |
670 |
6 |
10 |
0 |
18 |
11 |
1 |
| USA, MN |
789 |
|
583 |
4 |
17 |
|
10 |
11 |
1 |
| USA, CO |
600 |
0 |
482 |
2 |
20 |
|
11 |
10 |
1 |
| USA, MD |
468 |
0 |
314 |
1 |
11 |
0 |
10 |
3 |
1 |
| USA, TX |
441 |
0 |
328 |
3 |
12 |
|
13 |
6 |
2 |
| USA, NB |
374 |
|
253 |
|
6 |
|
6 |
3 |
1 |
| USA, MI |
344 |
|
178 |
|
|
1 |
5 |
7 |
|
| USA, MA |
319 |
0 |
227 |
1 |
7 |
0 |
4 |
3 |
1 |
| USA, NY |
319 |
0 |
226 |
1 |
2 |
1 |
12 |
5 |
0 |
| USA, IL |
310 |
|
199 |
|
16 |
0 |
8 |
1 |
|
| USA, MA |
270 |
1 |
181 |
2 |
12 |
0 |
10 |
1 |
0 |
| USA, PA |
225 |
1 |
155 |
2 |
11 |
0 |
4 |
2 |
2 |
| USA, MI |
216 |
|
118 |
|
2 |
|
3 |
1 |
|
| USA, MN |
206 |
1 |
141 |
0 |
3 |
0 |
5 |
3 |
1 |
| USA, WA |
194 |
1 |
130 |
0 |
1 |
|
5 |
1 |
|
| USA, PA |
189 |
0 |
130 |
1 |
2 |
1 |
5 |
0 |
2 |
| USA, MA |
177 |
1 |
121 |
3 |
7 |
|
4 |
1 |
1 |
| USA, MD |
142 |
1 |
|
|
1 |
|
1 |
1 |
|
| USA, NY |
133 |
0 |
63 |
2 |
6 |
0 |
2 |
1 |
0 |
| USA, TX |
130 |
|
99 |
|
6 |
|
4 |
1 |
|
| USA, NY |
82 |
0 |
61 |
3 |
2 |
0 |
2 |
1 |
0 |
| USA, LA |
56 |
0 |
39 |
0 |
0 |
0 |
1 |
0 |
0 |
| USA, CA |
34 |
|
28 |
|
|
|
2 |
|
|
| USA, MA |
30 |
0 |
23 |
0 |
0 |
0 |
0 |
0 |
0 |
| Total |
9792 |
19 |
6653 |
42 |
204 |
4 |
202 |
90 |
24 |
| Uncorrect Rate |
|
0.19% |
67.94% |
0.43% |
2.08% |
0.04% |
2.06% |
0.92% |
0.25% |
| Chromosome Denominator |
|
7595 |
9650 |
7798 |
9414 |
6251 |
9792 |
9314 |
7978 |
| Correct Rate |
|
0.25% |
68.94% |
0.54% |
2.17% |
0.06% |
2.06% |
0.97% |
0.30% |
Table 3-14. Reanalysis of Mutation Frequencies from the Cystic Fibrosis Genetic Analysis Consortium Data (Kazazian, 1994) - Continued
| CAN, Toro |
1034 |
0 |
3 |
0 |
2 |
5 |
4 |
10 |
8 |
| CAN, Que |
444 |
|
|
|
|
|
|
0 |
5 |
| CAN, Que |
66 |
0 |
|
|
0 |
|
|
0 |
1 |
| USA, IG |
1117 |
|
3 |
8 |
1 |
2 |
8 |
23 |
14 |
| USA, NC |
1083 |
|
|
9 |
0 |
5 |
20 |
20 |
15 |
| USA, MN |
789 |
|
|
|
|
|
|
4 |
12 |
| USA, CO |
600 |
|
|
|
|
|
2 |
5 |
5 |
| USA, MD |
468 |
0 |
|
|
0 |
1 |
1 |
13 |
5 |
| USA, TX |
441 |
|
|
|
1 |
1 |
0 |
3 |
6 |
| USA, NB |
374 |
|
|
|
|
|
|
1 |
4 |
| USA, MI |
344 |
2 |
|
|
|
|
|
|
|
| USA, MA |
|
|
|
|
|
|
|
11 |
3 |
| USA, NY |
319 |
|
|
|
0 |
|
1 |
4 |
3 |
| USA, IL |
310 |
|
|
|
1 |
|
1 |
1 |
6 |
| USA, MA |
270 |
|
|
|
|
|
3 |
4 |
5 |
| USA, PA |
225 |
|
|
|
0 |
|
|
6 |
2 |
| USA, MI |
216 |
|
|
|
|
|
|
0 |
4 |
| USA, MN |
206 |
|
|
|
|
|
|
3 |
6 |
| USA, WA |
194 |
|
|
|
|
|
|
|
0 |
| USA, PA |
189 |
0 |
0 |
0 |
0 |
0 |
2 |
6 |
6 |
| USA, MA |
177 |
|
|
|
|
|
|
11 |
2 |
| USA, MD |
142 |
|
|
|
|
|
|
|
|
| USA, NY |
133 |
|
|
|
0 |
|
2 |
3 |
5 |
| USA, TX |
130 |
|
|
|
|
|
|
1 |
2 |
| USA, NY |
82 |
|
|
|
|
|
|
0 |
2 |
| USA, LA |
56 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
| USA, CA |
34 |
|
|
|
|
|
|
|
|
| USA, MA |
30 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
| Total |
9792 |
2 |
8 |
17 |
5 |
14 |
44 |
129 |
122 |
| Uncorrect Rate |
|
0.02% |
0.08% |
0.17% |
0.05% |
0.14% |
0.45% |
1.32% |
1.25% |
| Chromosome Denominator |
|
2187 |
2426 |
3509 |
5471 |
4418 |
6050 |
9078 |
9272 |
| Correct Rate |
|
0.09% |
0.33% |
0.48% |
0.09% |
0.32% |
0.73% |
1.42% |
1.32% |
Appendix B. Mutation Frequencies for 25 CFTR Mutations According to a New Data Analysis from the Cystic Fibrosis Foundation Patient Database
Table 3-15 contains a listing of the summary data derived from the Cystic Fibrosis Foundation database for 1999 (Fitzsimmons S, personal communication 2001; Palomaki et al., 2002). The study design was described earlier. This table contains the ‘raw' data and the ‘best' estimate for mutation frequencies may be a derivation of these numbers.
Table 3-15. Mutation Frequencies in the United States for Three Racial/Ethnic in Therapeutic Development Network (TDN) Centers and All Centers (Cystic Fibrosis Foundation)
delF508 |
2,989 (75.90) |
18,441 (75.04) |
78 (60.00) |
869 (63.25) |
57 (47.50) |
460 (59.09) |
G542X |
94 (2.39) |
590 (2.40) |
11 (8.46) |
70 (5.09) |
5 (4.17) |
15 (1.72) |
G551D |
96 (2.44) |
608 (2.47) |
1 (0.77) |
11 (0.80) |
0 (0.00) |
16 (1.83) |
621+1G>T |
48 (1.22) |
227 (0.92) |
1 (0.77) |
7 (0.51) |
1 (0.83) |
9 (1.03) |
W1282X |
62 (1.57) |
364 (1.48) |
0 (0.00) |
10 (0.73) |
0 (0.00) |
4 (0.46) |
N1303K |
48 (1.22) |
324 (1.32) |
0 (0.00) |
23 (1.67) |
1 (0.83) |
6 (0.69) |
delI507 |
59 (1.50) |
384 (1.56) |
3 (2.31) |
69 (5.02) |
4 (3.33) |
34 (3.89) |
R553X |
30 (0.76) |
244 (0.99) |
2 (1.54) |
10 (0.73) |
3 (2.50) |
12 (1.37) |
R117H |
22 (0.56) |
157 (0.64) |
0 (0.00) |
3 (0.22) |
0 (0.00) |
1 (0.11) |
3849+10kbC>T |
17 (0.43) |
158 (0.65) |
3 (2.31) |
21 (1.53) |
1 (0.83) |
3 (0.34) |
2789+5G>A |
19 (0.48) |
86 (0.35) |
0 (0.00) |
3 (0.22) |
0 (0.00) |
0 (0.00) |
1717-1G>T |
16 (0.41) |
123 (0.50) |
0 (0.00) |
6 (0.44) |
0 (0.00) |
0 (0.00) |
R347P |
17 (0.43) |
66 (0.27) |
0 (0.00) |
3 (0.22) |
0 (0.00) |
1 (0.11) |
711+1G>T |
3 (0.08) |
26 (0.11) |
0 (0.00) |
5 (0.36) |
0 (0.00) |
0 (0.00) |
R560T |
18 (0.46) |
72 (0.29) |
0 (0.00) |
0 (0.00) |
0 (0.00) |
3 (0.34) |
A455E |
5 (0.13) |
43 (0.17) |
0 (0.00) |
0 (0.00) |
0 (0.00) |
0 (0.00) |
3569delC |
13 (0.36) |
71 (0.29) |
1 (0.77) |
2 (0.15) |
0 (0.00) |
1 (0.11) |
G85E |
8 (0.20) |
57 (0.23) |
0 (0.00) |
5 (0.36) |
0 (0.00) |
2 (0.23) |
R1162X |
14 (0.36) |
61 (0.25) |
0 (0.00) |
8 (0.58) |
1 (0.83) |
5 (0.57) |
2184delA |
9 (0.23) |
36 (0.15) |
0 (0.00) |
3 (0.22) |
0 (0.00) |
0 (0.00) |
1898+1G>A |
9 (0.23) |
47 (0.19) |
0 (0.00) |
0 (0.00) |
1 (0.83) |
1 (0.11) |
R334W |
6 (0.15) |
29 (0.12) |
2 (1.54) |
18 (1.31) |
0 (0.00) |
2 (0.23) |
I148T |
3 (0.08) |
15 (0.06) |
1 (0.77) |
1 (0.07) |
0 (0.00) |
0 (0.00) |
3120+1G>T |
2 (0.05) |
6 (0.02) |
0 (0.00) |
3 (0.22) |
8 (6.67) |
58 (6.64) |
1078delT |
0 (0.00) |
7 (0.03) |
0 (0.00) |
1 (0.07) |
0 (0.00) |
0 (0.00) |
Sub Total |
3,608 (91.62) |
22,243 (90.50) |
103 (79.24) |
1,151 (83.77) |
82 (68.33) |
633 (72.43) |
Other Identified |
62 (1.57) |
284 (1.16) |
7 (5.38) |
42 (3.06) |
14 (11.67) |
60 (6.86) |
Not Identified |
268 (6.81) |
2,049 (8.34) |
20 (15.38) |
181 (13.17) |
24 (20.00) |
181 (20.71) |
Total |
3,938 (100) |
24,576 (100) |
130 (100) |
1,374 (100) |
120 (100) |
874 (100) |
|
|
Page last reviewed: June 8, 2007 (archived document)
Page last updated: November 2, 2007
Content Source: National Office of Public Health Genomics |
|
|