ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4111G>T (p.Glu1371Ter) (rs397508675)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000047076 SCV000245913 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000047076 SCV000220975 likely pathogenic Cystic fibrosis 2014-12-22 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780149 SCV000917196 pathogenic not specified 2018-04-06 criteria provided, single submitter clinical testing Variant summary: CFTR c.4111G>T (p.Glu1371X) 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.c.4144C>T/p.Gln1382X). The variant allele was found at a frequency of 4.1e-06 in 246000 control chromosomes. c.4111G>T has been reported in the literature in individuals affected with Cystic Fibrosis. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar and classified the variant as likely pathogenic. CFTR2 database lists variant as a CF-causing variant with 19 patients with this variant in the database. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000047076 SCV001588143 pathogenic Cystic fibrosis 2019-09-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1371*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with cystic fibrosis (PMID: 1376017). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53891). This variant has been reported to affect the glycosylation of CFTR protein (PMID: 30444886). 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.
Natera, Inc. RCV000047076 SCV001454295 pathogenic Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

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