ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.14C>T (p.Pro5Leu) (rs193922501)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000029477 SCV000074336 uncertain significance Cystic fibrosis 2017-12-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 5 of the CFTR protein (p.Pro5Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs193922501, ExAC 0.005%). This variant has been reported in trans with a pathogenic variant in several individuals with mild respiratory symptoms, chronic pancreatitis and/or atypical cystic fibrosis (CF) (PMID: 21983161, 18306312, 17594398, 17594397, 25910067). This variant has also been reported in trans with a pathogenic variant in two asymptomatic and fertile adult males (PMID: 21983161) and multiple asymptomatic newborns (PMID: 17594398), which suggests that the p.Pro5Leu variant is not pathogenic. ClinVar contains an entry for this variant (Variation ID: 35824). Experimental studies have demonstrated that this missense variant results in decreased expression, partial mislocalization, and a reduction of channel activity of mature CFTR protein in cell culture (PMID: 18306312, 17235394). However, it is unclear from these studies if the effect of this missense on protein function is clinically significant. In summary, this variant is a rare missense change that has been shown to affect protein function in cell culture but the current clinical evidence for this variant is conflicting, with observations in both affected and unaffected individuals. Therefore, this change has been classified as a Variant of Uncertain Significance.
Counsyl RCV000029477 SCV000220159 likely pathogenic Cystic fibrosis 2014-03-13 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727666 SCV000854974 likely pathogenic not provided 2017-11-20 criteria provided, single submitter clinical testing
Mendelics RCV000029477 SCV000886149 likely pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004225 SCV001163101 likely pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV001009493 SCV001169588 pathogenic CFTR-related disorders 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001011889 SCV001172271 likely pathogenic Inborn genetic diseases 2019-09-23 criteria provided, single submitter clinical testing 2 of classification of c (below) met (2c = 1b);Deficient protein function by in vitro/ex vivo assay;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)
Integrated Genetics/Laboratory Corporation of America RCV000029477 SCV000052127 pathogenic Cystic fibrosis 2015-04-03 no assertion criteria provided clinical testing

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.