ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.263T>G (p.Leu88Ter) (rs397508412)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000046644 SCV000677618 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000046644 SCV000486032 likely pathogenic Cystic fibrosis 2016-03-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781278 SCV000919191 pathogenic not specified 2018-05-25 criteria provided, single submitter clinical testing Variant summary: CFTR c.263T>G (p.Leu88X) 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. The variant was absent in 245518 control chromosomes. c.263T>G has been reported in the literature in multiple individuals affected with Cystic Fibrosis (Savov 1995, Ko 2008, Tian 2016). 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000046644 SCV001580101 pathogenic Cystic fibrosis 2019-08-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu88*) 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 individuals with cystic fibrosis (PMID: 23302613, 18955805, 1284542). 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: 53534). 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.

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