ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1400T>C (p.Leu467Pro) (rs139573311)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000029476 SCV000071509 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Invitae RCV000029476 SCV000284994 pathogenic Cystic fibrosis 2019-10-07 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 467 of the CFTR protein (p.Leu467Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs139573311, ExAC 0.01%). This variant has been reported in many individuals affected with cystic fibrosis (PMID: 20510657, 23974870, 26708955). ClinVar contains an entry for this variant (Variation ID: 35823). Experimental studies have shown that this missense change disrupts CFTR protein maturation and chloride conduction function in cell culture (PMID: 23974870, 23891399). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724155 SCV000700724 pathogenic not provided 2017-04-24 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029476 SCV000915200 pathogenic Cystic fibrosis 2017-04-28 criteria provided, single submitter clinical testing The CFTR c.1400T>C (p.Leu467Pro) missense variant has been reported in at least three studies and is found in at least 16 patients with cystic fibrosis in a presumed compound heterozygous state with another pathogenic CFTR variant in a majority of the cases (Jambhekar et al. 2010; Sosnay et al. 2013; Schrijver et al. 2016). The p.Leu467Pro variant is reported at a frequency of 0.00023 in the overall population of the Exome Sequencing Project. Experimental studies in cell culture show the p.Leu467Pro variant disrupts CFTR protein maturation and chloride conduction (Van Goor et al. 2014, Sosnay et al. 2013). Based on the evidence, the p.Leu467Pro variant is classified as pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Baylor Genetics RCV001004452 SCV001163497 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000029476 SCV000052126 pathogenic Cystic fibrosis 2015-04-03 no assertion criteria provided clinical testing
Counsyl RCV000029476 SCV000485755 likely pathogenic Cystic fibrosis 2018-03-21 no assertion criteria provided clinical testing

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