ABCMdb

PMID: 21547743

Sosnay PR, Castellani C, Corey M, Dorfman R, Zielenski J, Karchin R, Penland CM, Cutting GR
Evaluation of the disease liability of CFTR variants.
Methods Mol Biol. 2011;742:355-72., [PubMed]

Sentences

No. Mutations Sentence Comment

77 ABCC7 p.Ile148Thr For example, the variant p.Ile148Thr was initially felt to be disease causing, but further examination found that the mutation occurred at a higher rate in healthy individuals undergoing carrier screening than in CF patients (26). Login to comment 78 ABCC7 p.Ile148Thr Subsequent studies revealed that most CF patients with p.Ile148Thr also carry the two amino acid deletion c.3067_3072del (27). Login to comment 79 ABCC7 p.Ile148Thr The latter mutation in isolation causes CF whereas p.Ile148Thr in isolation does not. Login to comment 81 ABCC7 p.Arg117His For example, the disease liability of the ACMG mutation p.Arg117His is dependent on polythymidine variants in the flanking exon (28). Login to comment 82 ABCC7 p.Arg117His When this mutation is associated with the "5T" polythymidine tract, p.Arg117His has a higher penetrance for CF, whereas longer polythymidine tracts ("7T" or "9T") are associated with obstructive azoospermia or no disease at all. Login to comment 140 ABCC7 p.Ile148Thr ABCC7 p.Phe508Cys The bioinformatic tools PolyPhen and SIFT have been employed to evaluate amino acid changes in CFTR, but made significant errors incorrectly identifying "known" neutral polymorphisms p.Phe508Cys and p.Ile148Thr as likely to be deleterious (58, 59). Login to comment