ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2739T>A (p.Tyr913Ter) (rs149790377)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000046670 SCV000245922 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Mendelics RCV000046670 SCV000886231 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004486 SCV001163531 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000046670 SCV001169507 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000046670 SCV001361657 pathogenic Cystic fibrosis 2019-08-16 criteria provided, single submitter clinical testing Variant summary: CFTR c.2739T>A (p.Tyr913X) 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. The variant allele was found at a frequency of 1.2e-05 in 251394 control chromosomes. c.2739T>A has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Schrijver_2005, Schrijver_2016, Ratkiewicz_2017, Harris_2015, deDios Caballero_2016, deBecdelivre_2011). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory and one expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both submitters have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000046670 SCV001589145 pathogenic Cystic fibrosis 2020-10-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 913 (p.Tyr913*) of the CFTR gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs149790377, ExAC 0.01%). This variant has been observed in an individual with cystic fibrosis (CF) (PMID: 15858154). ClinVar contains an entry for this variant (Variation ID: 53552). A different variant (c.2737_2738insG, also known as 2869insG) giving rise to the same protein effect observed here (p.Tyr913*) has also been reported in several individuals affected with CF (PMID: 1373935). Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV001509321 SCV001715956 pathogenic not provided 2019-11-18 criteria provided, single submitter clinical testing PVS1, PM2, PP5
Counsyl RCV000046670 SCV001132358 likely pathogenic Cystic fibrosis 2015-04-30 no assertion criteria provided clinical testing

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