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Cystic fibrosis testing in a referral laboratory: results and lessons from a six-year period

Perry G Ridge125*, Christine Miller35, Pinar Bayrak-Toydemir145, D Hunter Best145, Rong Mao145, Jeffrey J Swensen145, Elaine Lyon145 and Karl V Voelkerding145

Author Affiliations

1 ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA

2 Department of Biology, Brigham Young University, Provo, UT, USA

3 ARUP Laboratories, Salt Lake City, UT, USA

4 Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA

5 500 W Chipeta Way, Salt Lake City, UT, 84108, USA

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Journal of Clinical Bioinformatics 2013, 3:3  doi:10.1186/2043-9113-3-3

Published: 23 January 2013



The recent introduction of high throughput sequencing technologies into clinical genetics has made it practical to simultaneously sequence many genes. In contrast, previous technologies limited sequencing based tests to only a handful of genes. While the ability to more accurately diagnose inherited diseases is a great benefit it introduces specific challenges. Interpretation of missense mutations continues to be challenging and the number of variants of uncertain significance continues to grow.


We leveraged the data available at ARUP Laboratories, a major reference laboratory, for the CFTR gene to explore specific challenges related to variant interpretation, including a focus on understanding ethnic-specific variants and an evaluation of existing databases for clinical interpretation of variants. In this study we analyzed 555 patients representing eight different ethnic groups. We observed 184 different variants, most of which were ethnic group specific. Eighty-five percent of these variants were present in the Cystic Fibrosis Mutation Database, whereas the Human Mutation Database and dbSNP/1000 Genomes had far fewer of the observed variants. Finally, 21 of the variants were novel and we report these variants and their clinical classifications.


Based on our analyses of data from six years of CFTR testing at ARUP Laboratories a more comprehensive, clinical grade database is needed for the accurate interpretation of observed variants. Furthermore, there is a particular need for more and better information regarding variants from individuals of non-Caucasian ethnicity.

Cystic fibrosis; CFTR; Novel variants; Next-generation sequencing; Interpretation of variants