ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2175dup (p.Glu726Argfs) (rs746418935)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007605 SCV000071474 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000007605 SCV000677922 pathogenic Cystic fibrosis 2015-06-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727574 SCV000854813 pathogenic not provided 2018-01-19 criteria provided, single submitter clinical testing
Mendelics RCV000007605 SCV000886215 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781235 SCV000919140 pathogenic not specified 2018-08-17 criteria provided, single submitter clinical testing Variant summary: CFTR c.2175dupA (p.Glu726ArgfsX4) 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 (eg., p.Leu732X and p.Arg764X). The variant allele was found at a frequency of 1.9e-05 in 1055458 control chromosomes. This frequency is not higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (1.9e-05 vs 0.013), allowing no conclusion about variant significance. c.2175dupA has been reported in the literature as a homozygous and compound heterozygous allele in numerous individuals affected with Cystic Fibrosis. 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, which showed <10% of normal CFTR mRNA in patient cells (Smit_1993). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000007605 SCV000027806 pathogenic Cystic fibrosis 1993-01-01 no assertion criteria provided literature only

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