ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1364C>A (p.Ala455Glu) (rs74551128)

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Total submissions: 9
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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
Counsyl RCV000007531 SCV000485215 pathogenic Cystic fibrosis 2015-11-27 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 absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
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.
Invitae RCV000007531 SCV000074294 pathogenic Cystic fibrosis 2018-08-01 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.
Mendelics RCV000007531 SCV000886236 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
OMIM RCV000007531 SCV000027732 pathogenic Cystic fibrosis 1990-11-01 no assertion criteria provided literature only
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.

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