ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1477C>T (p.Gln493Ter) (rs77101217)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007526 SCV000071546 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Integrated Genetics/Laboratory Corporation of America RCV000007526 SCV000696845 pathogenic Cystic fibrosis 2016-04-14 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a nonsense change involving a conserved nucleotide resulting in a predicted truncated CFTR protein, a known mechanism for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121326 (1/60663), which does not exceed the predicted maximum expected allele frequency for a pathogenic CFTR variant of 1/77. The variant of interest has been reported in multiple affected individuals via publications, along with multiple reputable clinical laboratories/databases cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727628 SCV000854904 pathogenic not provided 2018-08-15 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000999860 SCV000883566 pathogenic not specified 2019-03-21 criteria provided, single submitter clinical testing The CFTR c.1477C>T, p.Gln493Ter variant (rs77101217) has been reported in cystic fibrosis patients, often associated with pancreatic insufficiency (Kerem 1990, Ooi 2012, Sosnay 2013, CFTR2 database). It is listed in ClinVar (Variation ID: 7107), and observed in the general population databases at a frequency of 0.02 percent in the Exome Variant Server (2/13006 alleles), and 0.002 percent in the Genome Aggregation Database (6/277042 alleles). The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as severely pathogenic. References: CFTR2 database: Kerem B et al. (1990) Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 87(21):8447-51. Ooi C. et al. (2012) Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 11(5):355-62. Sosnay PR et al. (2013) Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 45(10):1160-7.
Illumina Clinical Services Laboratory,Illumina RCV000007526 SCV000915201 pathogenic Cystic fibrosis 2017-08-15 criteria provided, single submitter clinical testing The CFTR c.1477C>T (p.Gln493Ter) stop-gained variant has been reported in at least four studies and is found in a total of six affected individuals including four compound heterozygotes, one complex heterozygote, and one presumed heterozygote (Kerem et al. 1990; Kristidis et al. 1992; Feuillet-Fieux et al. 2011; Steiner et al. 2011). Three of the compound heterozygotes have a clinical diagnosis of cystic fibrosis and pancreatic insufficiency and have the p.Phe508del variant as their second variant (Kristidis et al. 1992). Steiner et al. (2011) reported on a compound heterozygote with a diagnosis of congenital bilateral absence of the vas deferens. Feuillet-Fieux et al. (2011) identified a complex heterozygous individual, with a clinical diagnosis of cystic fibrosis based on sweat chloride values who had no other pulmonary or intestinal symptoms, who carried three other variants on the maternal allele and the p.Gln493Ter variant on the paternal allele. The p.Gln493Ter variant was absent from 2456 controls and is reported at a frequency of 0.000047 in the European (non-Finnish) population of the Genome Aggregation Database. Due to the potential impact of stop-gained variants and the evidence available, the p.Gln493Ter 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 RCV001004456 SCV001163501 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000007526 SCV001169485 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000007526 SCV001194164 pathogenic Cystic fibrosis 2019-11-11 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.1477C>T(Q493*) 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 18456578. Classification of NM_000492.3(CFTR):c.1477C>T(Q493*) 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
Johns Hopkins Genomics,Johns Hopkins University RCV000007526 SCV001425421 pathogenic Cystic fibrosis 2020-04-22 criteria provided, single submitter clinical testing Disease-causing CFTR variant. See for phenotype information.
OMIM RCV000007526 SCV000027727 pathogenic Cystic fibrosis 1990-11-01 no assertion criteria provided literature only

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