ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1647T>G (p.Ser549Arg) (rs121909005)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000056350 SCV000087508 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000056350 SCV000485210 pathogenic Cystic fibrosis 2015-11-27 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000056350 SCV000891675 pathogenic Cystic fibrosis 2017-12-30 criteria provided, single submitter curation
Fulgent Genetics,Fulgent Genetics RCV000763573 SCV000894412 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000056350 SCV000696858 pathogenic Cystic fibrosis 2016-12-08 criteria provided, single submitter clinical testing Variant summary: The CFTR c.1647T>G (p.Ser549Arg) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 120694 control chromosomes and was reported in numerous affected individuals in the literature. Functional studies show the variant to result in defective channel gating as the predominant defect, resulting in less than 1% chloride conductance compared to WT (Yu_2012, Sosnay_2013). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, including CFTR2. Ivacaftor addition caused a >10-fold increase in CFTR-mediated chloride transport in FRT cells expressing S549R-CFTR (Yu_2012) and this drug has been approved by the U.S. Food and Drug Administration to treat patients with CF who are 2 years and older with at least one copy of this mutation (CFTR2 database). Taken together, this variant is classified as pathogenic.
Mendelics RCV000056350 SCV000886187 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
PharmGKB RCV000211129 SCV000268176 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508411 SCV000601054 pathogenic not provided 2017-06-08 criteria provided, single submitter clinical testing

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