ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2249C>T (p.Pro750Leu) (rs140455771)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000078984 SCV000603030 uncertain significance not provided 2017-05-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000078984 SCV000281655 likely pathogenic not provided 2014-11-13 criteria provided, single submitter clinical testing
Counsyl RCV000675059 SCV000800517 uncertain significance Cystic fibrosis 2017-04-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078984 SCV000110852 uncertain significance not provided 2017-11-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000675059 SCV000915207 likely pathogenic Cystic fibrosis 2018-11-30 criteria provided, single submitter clinical testing The CFTR c.2249C>T (p.Pro750Leu) missense variant has been reported in three studies and in a total of three patients with CFTR-related disorders, all in a compound heterozygous state (Orozco et al. 2000; Storm et al. 2007; Li et al. 2012). Phenotypes included cystic fibrosis including pancreatic insufficiency, classic CF, and congenital absence of the vas deferens and the variant on the second allele was p.Phe508del in at least two of the patients. Control data are unavailable for this variant, which is reported at a frequency of 0.0007 in the European American population of the Exome Sequencing Project. Based on the evidence, the p.Pro750Leu variant is classified as likely pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Integrated Genetics/Laboratory Corporation of America RCV000078984 SCV000696892 uncertain significance not provided 2017-06-26 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2249C>T (p.Pro750Leu) missense variant involves the alteration of a conserved nucleotide, is located in regulator domain in CFTR protein (InterPro), and 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 28/120846 control chromosomes from ExAC at a frequency of 0.0002317, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in 2 CF patients and 1 CBAVD patient with a pathogenic CFTR variant on the other chromosome (Orozco_HG_2000, Li_JCF_2012, Prontera_PHG_2016). This variant also has been reported in a neonate with borderline sweat chloride level who carried delF508 in other allele and p.Arg352Trp in the same allele (McGinniss_HG_2005). Therefore, clinical evidence does not unequivocally support causality of this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic or uncertain significance. Taken together, this variant is classified as 'VUS-possibly pathogenic'.
Mendelics RCV000675059 SCV000886150 likely pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing

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