ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1364C>A (p.Ala455Glu) (rs74551128)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
American College of Medical Genetics and Genomics (ACMG) RCV000007531 SCV000071390 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
CFTR2 RCV000007531 SCV000071495 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
PharmGKB RCV000660853 SCV000783092 drug response ivacaftor response - Efficacy 2018-03-23 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.
Invitae RCV000007531 SCV000074294 pathogenic Cystic fibrosis 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 455 of the CFTR protein (p.Ala455Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is present in population databases (rs74551128, ExAC 0.008%). This variant has been reported numerous times in the literature in individuals affected with cystic fibrosis (PMID: 2236053, 23974870, 15371902, 23466340). ClinVar contains an entry for this variant (Variation ID: 7111). Experimental studies have shown that this variant significantly reduces the amount of functioning CFTR protein (PMID: 7542778, 23974870). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000007531 SCV000696836 pathogenic Cystic fibrosis 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The CFTR c.1364C>A (p.Ala455Glu) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. These predictions were confirmed by functional studies showing the variant to result in <10% chloride conductance (Sosnay_2013). This variant was found in 4/94982 control chromosomes at a frequency of 0.0000421, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant has been reported in numerous affected individuals in the literature and is a known common disease causing mutation. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics RCV000007531 SCV000886236 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763569 SCV000894408 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 RCV001004446 SCV001163491 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000007531 SCV001169478 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000007531 SCV001194086 pathogenic Cystic fibrosis 2019-11-12 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.1364C>A(A455E) is classified as pathogenic in the context of cystic fibrosis and is associated with the non-classic form of disease. Sources cited for classification include the following: PMID 23974870. Classification of NM_000492.3(CFTR):c.1364C>A(A455E) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Johns Hopkins Genomics,Johns Hopkins University RCV000007531 SCV001430619 pathogenic Cystic fibrosis 2020-07-24 criteria provided, single submitter clinical testing Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
OMIM RCV000007531 SCV000027732 pathogenic Cystic fibrosis 1990-11-01 no assertion criteria provided literature only

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