Table 2.
CFTR variants found in 26 cases that underwent open chart review
| Variant cDNA name | Variant protein name | CFTR2 (8/31/18) | ClinVar Review Statusa | ClinVar link (accessed 9/15/18) | # alleles in compound heterozygous | # alleles in homozygous | # alleles | ||
|---|---|---|---|---|---|---|---|---|---|
| 1 | c.115 C > T | p.Gln39Ter | Q39X | CF causing | Pathogenic *3 | https://www.ncbi.nlm.nih.gov/clinvar/23273455/ | 1 | 0 | 1 |
| 2 | c.263 T > G | p.Leu88Ter | L88X | CF causing | Pathogenic *3 | https://www.ncbi.nlm.nih.gov/clinvar/variation/53534/ | 1 | 0 | 1 |
| 3 | c.350 G > A | p.Arg117His | R117H | Varying clinical consequence | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007528/ | 1 | 0 | 1 |
| 4 | c.489 + 1 G > T | NA | NA | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000043565/ | 1 | 0 | 1 |
| 5 | c.617 T > G | p.Leu206Trp | L206W | CF causing | Pathogenic *3 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007611/ | 2 | 0 | 2 |
| 6 | c.1000 C > T | p.Arg334Trp | R334W | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007559/ | 1 | 0 | 1 |
| 7 | c.1521_1523delCTT | p.Phe508del | F508del | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007523/ | 10 | 28 | 38 |
| 8 | c.1624G > T | p.Gly542Ter | G542X | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007535/ | 1 | 0 | 1 |
| 9 | c.1652G > A | p.Gly551Asp | G551D | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007540/ | 1 | 0 | 1 |
| 10 | c.2128 A > T | p.Lys710Ter | K710X | CF causing | Pathogenic *3 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007624/ | 1 | 0 | 1 |
| 11 | c.3705 T > G | p.Ser1235Arg | S1235R | Non CF-causing | Benign | https://www.ncbi.nlm.nih.gov/clinvar/RCV000029527/ | 1 | 0 | 1 |
| 12 | c.3717 G > C | p.Arg1239Ser | R1239S | NA | NA | NA | 1 | 0 | 1 |
| 13 | c.3718–2477 C > T | NA | NA | CF causing | Pathogenic *4 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000007586/ | 1 | 0 | 1 |
| 14 | c.4426 C > T | p.Gln1476Ter | Q1476X | NA | Pathogenic *2 | https://www.ncbi.nlm.nih.gov/clinvar/RCV000047135/ | 1 | 0 | 1 |
| 24 | 28 | 52 | |||||||
Variants #11 (S1235R) and #12 (R1239S) were identified in cases 23 and 22, respectively (see Table 1), in each case forming CFTR compound heterozygotes with F508del; however, neither variant was found as pathogenic variants in either the CFTR2 or ClinVar databases. Variant #14 was missed on clinical testing obtained in 2009 for case 26 (see Table 1). Note that only 42% (5/12) of the pathogenic variants in this table were included in the 2004 ACMG panel #3, 6, 7, 8, 9. The genomic screening used in this manuscript (WES plus microarray) is more sensitive than many of the clinical genetic tests offered in the past. aClinVar review status: *2 = endorsed by two or more submitters providing assertion criteria provided the same interpretation, *3 = endorsed by expert panel, *4 = endorsed by practice guideline