ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.14C>T (p.Pro5Leu) (rs193922501)

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Total submissions: 5
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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
Integrated Genetics/Laboratory Corporation of America RCV000029477 SCV000052127 pathogenic Cystic fibrosis 2015-04-03 no assertion criteria provided clinical testing

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