ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1521_1523delCTT (p.Phe508delPhe) (rs113993960)

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Total submissions: 30
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000058929 SCV000602968 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624683 SCV000741228 pathogenic Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
American College of Medical Genetics and Genomics (ACMG) RCV000007523 SCV000071392 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
Blueprint Genetics, RCV000058929 SCV000928113 pathogenic not provided 2018-12-12 criteria provided, single submitter clinical testing
CFTR2 RCV000007523 SCV000071493 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000058929 SCV000511517 pathogenic not provided 2016-10-28 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626692 SCV000747395 likely pathogenic Duodenal stenosis 2017-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626693 SCV000747396 pathogenic Recurrent pancreatitis 2017-01-01 criteria provided, single submitter clinical testing
Counsyl RCV000007523 SCV000678175 pathogenic Cystic fibrosis 2015-04-15 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000007523 SCV000891676 pathogenic Cystic fibrosis 2017-12-30 criteria provided, single submitter clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000007523 SCV000536740 pathogenic Cystic fibrosis 2016-06-10 no assertion criteria provided research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000007523 SCV000225226 pathogenic Cystic fibrosis 2017-01-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000058929 SCV000330918 pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000007523 SCV000883108 pathogenic Cystic fibrosis 2018-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000058929 SCV000329246 pathogenic not provided 2018-07-30 criteria provided, single submitter clinical testing The c.1521_1523delCTT pathogenic variant in the CFTR gene (also known as p.Phe508del or delta F508) is the most common variant identified in the CFTR gene, with up to 90% of individuals with cystic fibrosis (CF) having at least one copy of the c.1521_1523delCTT variant (Cai et al., 2011). The c.1521_1523delCTT variant results in an in-frame deletion of a single Phenylalanine residue at codon 508. Individuals who are homozygous for the c.1521_1523delCTT variant demonstrate the classic features of CF, whereas individuals compound heterozygous for the c.1521_1523delCTT variant and another CFTR variant may have a modified disease phenotype (Ong et al., 2017). Heterozygous carriers of the c.1521_1523delCTT variant are usually asymptomatic, however, may be at increased risk for developing a CFTR-related disorder, as an increased prevalence of single CFTR pathogenic variants has been observed among individuals with chronic pulmonary conditions, CAVD and pancreatitis (Cuppens et al., 2004; Bombieri et al., 2011). We interpret the c.1521_1523delCTT variant as a pathogenic variant.
GeneReviews RCV000119038 SCV000153744 pathogenic Hereditary pancreatitis 2014-03-13 no assertion criteria provided literature only
Genetic Services Laboratory, University of Chicago RCV000007523 SCV000594089 pathogenic Cystic fibrosis 2016-08-26 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000007523 SCV000607274 not provided Cystic fibrosis no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
HudsonAlpha Institute for Biotechnology RCV000007523 SCV000584079 pathogenic Cystic fibrosis 2013-10-21 criteria provided, single submitter research
Invitae RCV000007523 SCV000074347 pathogenic Cystic fibrosis 2018-07-07 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 11 of the CFTR mRNA (c.1521_1523delCTT). This leads to the deletion of one amino acid residue in the CFTR protein (p.Phe508del) but otherwise preserves the integrity of the reading frame. This single amino acid deletion (also known as ∆F508) disrupts protein function and is the most common cause of cystic fibrosis (PMID: 2475911, 15371902, 23974870). For these reasons, it has been classified as Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000007523 SCV000864219 pathogenic Cystic fibrosis 2019-01-15 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000007523 SCV000538017 pathogenic Cystic fibrosis 2016-03-30 criteria provided, single submitter clinical testing The c.1521_1523delCTT (p.Phe508del), also known as ΔF508, is an in-frame deletion in the CFTR gene. This variant is the most common CF-causing mutation, accounting for an estimated 72% of mutant alleles in people of European ancestry (Watson et al., 2004). This p.Phe508del variant is classified as a class II mutation that blocks the processing of the CFTR protein (Welsh et al., 2001). This variant has been reported at low frequencies (1.0%) in 1000 Genomes and ExAc population databases, but has not been reported in the Exome Sequencing Project database (ESP). The CFTR2 database has 32,833 patients that have this mutation, which they classify as CF-causing (http://www.cftr2.org/mutation.php?view=general&mutation_id=1). Therefore, this collective evidence supports the classification of the c.1521_1523delCTT (p.Phe508del) as a recessive pathogenic variant for Cystic fibrosis.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000007523 SCV000221179 pathogenic Cystic fibrosis 2017-05-13 criteria provided, single submitter clinical testing The p.Phe508del variant in CFTR (also known as ΔF508) is a deletion of a single amino acid at position 508 and is well-established as a pathogenic variant for cystic fibrosis in an autosomal recessive manner (Kerem 1989, Fuller 1992, Southern 1997, Grody 2001, Sosnay 2013). The p.Phe508del variant is the most common pathogenic variant reported in CFTR and is included in the ACMG Technical Standards and Guidelines for CFTR Mutation Testing (http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm).
Mendelics RCV000007523 SCV000886152 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
OMIM RCV000007523 SCV000027724 pathogenic Cystic fibrosis 2015-05-17 no assertion criteria provided literature only
OMIM RCV000007524 SCV000053487 risk factor Bronchiectasis with or without elevated sweat chloride 1, modifier of 2015-05-17 no assertion criteria provided literature only
PharmGKB RCV000211188 SCV000268159 drug response ivacaftor response - Efficacy 2018-03-27 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.
PharmGKB RCV000417138 SCV000494683 drug response ivacaftor / lumacaftor response - Efficacy 2018-03-28 reviewed by expert panel curation PharmGKB Level of Evidence 1B: Annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more than one cohort with significant p-values, and preferably will have a strong effect size.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000058929 SCV000889288 pathogenic not provided 2016-02-05 criteria provided, single submitter clinical testing
SNPedia RCV000058929 SCV000090450 not provided not provided no assertion provided not provided

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