ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.577G>T (p.Glu193Ter) (rs397508759)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000047199 SCV000245936 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000047199 SCV000221027 likely pathogenic Cystic fibrosis 2015-01-15 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000506873 SCV000331309 pathogenic not provided 2014-08-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506873 SCV000602969 pathogenic not provided 2017-09-27 criteria provided, single submitter clinical testing The CFTR c.577G>T, p.Glu193Ter variant (rs397508759) has been reported in multiple cystic fibrosis patients, and often associated with pancreatic insufficiency (Ooi 2012, Terlizzi 2014, CFTR2 database). It is listed in ClinVar (Variation ID: 54007), but not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). 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: http://cftr2.org/ Ooi C. et al. (2012) Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 11(5):355-62. Terlizzi V et al. (2014) Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis. J Cyst Fibros. 13(5):579-84.
Fulgent Genetics,Fulgent Genetics RCV000763154 SCV000893741 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
CFTR-France RCV000047199 SCV001169303 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000047199 SCV001437228 pathogenic Cystic fibrosis 2020-09-08 criteria provided, single submitter clinical testing Variant summary: CFTR c.577G>T (p.Glu193X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 250106 control chromosomes. c.577G>T has been reported in the literature in multiple individuals affected with Cystic Fibrosis and CFTR-related disorders (example, Claustres_2000, Dorfman_2010, Ooi_2012, Amato_2012, Loubieres_2002). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic (n=4)/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000047199 SCV001585099 pathogenic Cystic fibrosis 2019-06-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu193*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with cystic fibrosis or recurrent pancreatitis (PMID: 22658665, 22020151). ClinVar contains an entry for this variant (Variation ID: 54007). Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.

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