ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2125C>T (p.Arg709Ter) (rs121908760)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000056359 SCV000071553 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Integrated Genetics/Laboratory Corporation of America RCV000056359 SCV000696887 pathogenic Cystic fibrosis 2017-06-23 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2125C>T (p.Arg709X) variant results in a premature termination codon, predicted to cause a truncated or absent CFTR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.3266G>A/p.Trp1089X, c.3276C>A/p.Tyr1092X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/119868 control chromosomes at a frequency of 0.0000167, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in multiple CF patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727640 SCV000854925 pathogenic not provided 2018-05-31 criteria provided, single submitter clinical testing
Mendelics RCV000056359 SCV000886260 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000727640 SCV001134125 pathogenic not provided 2018-11-14 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data at a frequency consistent with pathogenicity. Occurs in multiple cases with a recessive pathogenic variant in the same gene.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000919 SCV001158006 pathogenic not specified 2018-11-20 criteria provided, single submitter clinical testing The CFTR c.2125C>T; p.Arg709Ter variant (rs121908760) is reported in the literature in multiple individuals affected with pancreatic insufficient cystic fibrosis (Sosnay 2013, CFTR2 database, ABCC7 Mutation database and references therein). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 53440), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Arg709Ter variant is considered to be pathogenic. References: Link to CFTR2 database: https://cftr2.org/mutation/scientific/pi/R709X Link to ABCC7 (CFTR) Mutation database: http://abcmutations.hegelab.org/mutationDetails?id=4542 Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 Oct;45(10):1160-7.
Baylor Genetics RCV001004468 SCV001163513 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000056359 SCV001169540 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000056359 SCV001193956 pathogenic Cystic fibrosis 2019-12-04 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.2125C>T(R709*) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 23974870, 7535742 and 22658665. Classification of NM_000492.3(CFTR):c.2125C>T(R709*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.

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