ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.296C>T (p.Pro99Leu)

gnomAD frequency: 0.00001  dbSNP: rs397508467
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000577122 SCV000924243 pathogenic Cystic fibrosis 2017-12-08 reviewed by expert panel research
CFTR-France RCV001009535 SCV001169630 pathogenic Cystic fibrosis; CFTR-related disorder 2018-03-09 criteria provided, single submitter curation the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both
Labcorp Genetics (formerly Invitae), Labcorp RCV000577122 SCV001576101 likely pathogenic Cystic fibrosis 2024-02-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 99 of the CFTR protein (p.Pro99Leu). This variant is present in population databases (rs397508467, gnomAD 0.002%). This missense change has been observed in individuals with cystic fibrosis (PMID: 11732487, 14872121). ClinVar contains an entry for this variant (Variation ID: 53610). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CFTR function (PMID: 8663008, 29805046). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare RCV000577122 SCV005873748 pathogenic Cystic fibrosis 2021-05-29 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577122 SCV000679420 not provided Cystic fibrosis no assertion provided literature only

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