ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4232A>C (p.Gln1411Pro) (rs150177304)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589528 SCV000697013 uncertain significance not provided 2016-12-21 criteria provided, single submitter clinical testing Variant summary: The c.4232A>C (p.Gln1411Pro) in CFTR gene is a missense change that involves a mildly conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant of interest is located within AAA+ ATPase domain functional domain and several neighboring variants have been associated with CF, although the functional impact of this missense change is yet to be studied. The variant is present in the large control population dataset of ExAC at a frequency 0.0000166 (2/120320 chrs tested), exclusively in individuals of Latino descent (0.00017; 2/11398) which does not exceed the maximal expected frequency of a pathogenic allele (0.013) in this gene. This variant was identified in a population screening of patients with primary sclerosing cholangitis and inflammatory bowel syndromes (Sickkids db). The variant has not, to our knowledge, been reported in affected individual via published reports or classified by a reputable database/clinical laboratory. At this time there is not sufficient undeniable evidence to classify this variant with confidence. Taken together, the variant was classified as VUS until more data becomes available.
Invitae RCV000697105 SCV000825699 uncertain significance Cystic fibrosis 2018-06-07 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 1411 of the CFTR protein (p.Gln1411Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is present in population databases (rs150177304, ExAC 0.02%). This variant has not been reported in the literature in individuals with CFTR-related disease. ClinVar contains an entry for this variant (Variation ID: 495947). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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