ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.330C>A (p.Asp110Glu) (rs397508537)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577359 SCV000679435 not provided Cystic fibrosis no assertion provided literature only
Counsyl RCV000577359 SCV000796470 uncertain significance Cystic fibrosis 2017-12-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000596840 SCV000708644 pathogenic not provided 2017-05-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000577359 SCV000696964 pathogenic Cystic fibrosis 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The CFTR c.330C>A (p.Asp110Glu) variant located in the first extracellular loop (ECL1 via Cui_2014) involves the alteration of a non-conserved nucleotide and 3/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 120396 control chromosomes. Multiple publications cite the variant in affected individuals with varying phenotypes, predominantly presenting as a mild phenotype, which patients have a borderline sweat chloride level, pancreatic sufficiency, and normal lung function. However, functional studies have indicated that the variant greater affects chloride transport (van Goor_2013) and significantly longer mean burst durations (Cui_2014 and Infield_2016). Authors further go on to state "the structure of ECL1 must be tuned delicately to maintain function...none of the charge-retaining mutations identified in ECL1 are able to completely rescue the mutant channel behavior to that of WT-CFTR. This is likely the result of a requirement for very specific bond angles within a network of charged residues that control the architecture of ECL1"(Cui_2014)." Furthermore, another variant at this location D110H has been classified as "pathogenic" by LCA, along with another variant being reported D110R (Cui_2014), therefore, suggesting this location is a mutational hotspot and important for protein function. The variant of interest has been reported by multiple databases but without a clear classification being provided. Therefore, due to the functional impact of the variant via studies, located in a function domain and mutational hotspot, the variant of interest has been classified as "pathogenic."
PharmGKB RCV000660830 SCV000783069 drug response ivacaftor response - Efficacy 2018-03-22 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.