ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3472C>T (p.Arg1158Ter) (rs79850223)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007564 SCV000071550 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
GeneDx RCV000579152 SCV000680709 pathogenic not provided 2017-06-16 criteria provided, single submitter clinical testing The R1158X variant in the CFTR gene has been reported previously in association with cystic fibrosis (Ronchetto et al., 1992; Frossard et al., 2000; Ooi et al., 2012; Sosnay et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1158X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R1158X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000007564 SCV000696972 pathogenic Cystic fibrosis 2016-09-28 criteria provided, single submitter clinical testing Variant summary: The CFTR c.3472C>T (p.Arg1158X) 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 in CF or CFTR-related diseases. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Arg1162X, p.Gln1382X, p.Ser1455X, etc.). This variant was found in 5/120064 control chromosomes at a frequency of 0.0000416, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported in many affected individuals with CF and CF-RDs (Amato_2012, Sosnay_2013). Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000579152 SCV000883575 pathogenic not provided 2017-10-04 criteria provided, single submitter clinical testing The CFTR c.3472C>T; p.Arg1158Ter variant is reported in the medical literature in individuals with cystic fibrosis and related disorders (Amato 2012, Frossard 2000, Ooi 2012, Sosnay 2013). The variant is listed in the ClinVar database (Variation ID: 7144), in the dbSNP variant database (rs79850223), and in the Genome Aggregation Database with a low population frequency (8/245236 alleles). This variant introduces a premature termination codon and is predicted to result in a truncated protein or mRNA subject to non-sense mediated decay. Considering available information, this variant is classified as severely pathogenic. References: Amato F et al. Extensive molecular analysis of patients bearing CFTR-related disorders. J Mol Diagn. 2012 Jan;14(1):81-9. Frossard PM et al. Mild clinical phenotype associated with R1158X/S549R(T-->G) CFTR genotype. Clin Genet. 2000 Aug;58(2):147-9. Ooi CY and Durie PR. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012 Sep;11(5):355-62. 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.
Mendelics RCV000007564 SCV000886237 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763158 SCV000893745 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004499 SCV001163544 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000007564 SCV001169264 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Ambry Genetics RCV001020386 SCV001181859 pathogenic Inborn genetic diseases 2018-12-06 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Myriad Women's Health, Inc. RCV000007564 SCV001194162 pathogenic Cystic fibrosis 2019-11-11 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.3472C>T(R1158*) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID 23974870 and 21909392. Classification of NM_000492.3(CFTR):c.3472C>T(R1158*) 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.‚Äã
OMIM RCV000007564 SCV000027765 pathogenic Cystic fibrosis 1992-02-01 no assertion criteria provided literature only

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