ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.825C>G (p.Tyr275Ter) (rs193922532)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000029545 SCV000677629 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Integrated Genetics/Laboratory Corporation of America RCV000029545 SCV000052197 pathogenic Cystic fibrosis 2019-02-04 criteria provided, single submitter clinical testing Variant summary: The variant, CFTR c.825C>G (p.Tyr275X) 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 (e.g. c.828C>A (p.Cys276X), c.988G>T(p.Gly330X)). The variant was absent in 244008 control chromosomes (gnomAD) and has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Bernardino 2000, McGinniss 2005, Claustres 2017, Dankert-Roelse 2018). These data indicate that the variant is likely to be associated with disease. At least one publication reported experimental evidence, evaluating the basal and drug induced read-through levels of this premature termination codon, and reported less than 0.5% basal read-through activities and low levels of drug induced responses (Pranke 2018). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Mendelics RCV000029545 SCV000886287 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004239 SCV001163115 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000029545 SCV001169333 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Counsyl RCV000029545 SCV001132150 likely pathogenic Cystic fibrosis 2017-09-22 no assertion criteria provided clinical testing

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