ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1055G>A (p.Arg352Gln) (rs121908753)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007619 SCV000071522 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
PharmGKB RCV000660773 SCV000783012 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.
Mendelics RCV000007619 SCV000886259 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763568 SCV000894407 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
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985669 SCV001134107 pathogenic not provided 2019-04-13 criteria provided, single submitter clinical testing The best available variant frequency is uninformative. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Occurs in multiple cases with a recessive pathogenic variant in the same gene. Assessment of experimental evidence suggests this variant results in abnormal protein function.
Baylor Genetics RCV001004254 SCV001163130 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000007619 SCV001169460 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000007619 SCV001193913 pathogenic Cystic fibrosis 2019-11-12 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.1055G>A(R352Q) 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 18456578 and 23974870. Classification of NM_000492.3(CFTR):c.1055G>A(R352Q) 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.‚Äã
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000007619 SCV001360485 pathogenic Cystic fibrosis 2019-10-07 criteria provided, single submitter clinical testing Variant summary: CFTR c.1055G>A (p.Arg352Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251124 control chromosomes (gnomAD). c.1055G>A has been reported in the literature in multiple individuals affected with Cystic Fibrosis (e.g. Dupuis_2015, Shackelton_1994, Sosnay_2013). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, and demonstrated that the variant leads to defective chloride channel function (Sosnay 2013). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Johns Hopkins Genomics, Johns Hopkins University RCV000007619 SCV001371785 pathogenic Cystic fibrosis 2020-01-06 criteria provided, single submitter clinical testing Previously reported disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Invitae RCV000007619 SCV001579707 pathogenic Cystic fibrosis 2020-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 352 of the CFTR protein (p.Arg352Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs121908753, ExAC 0.01%). This variant has been observed in combination with another CFTR variant in individuals affected with cystic fibrosis (PMID: 27086061, 7544319, 28646244, 20522854). ClinVar contains an entry for this variant (Variation ID: 7198). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007619 SCV000027820 pathogenic Cystic fibrosis 1993-01-01 no assertion criteria provided literature only

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