ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.535C>A (p.Gln179Lys) (rs367850319)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000590474 SCV000697034 uncertain significance not provided 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The CFTR c.535C>A (p.Gln179Lys) variant affects a conserved nucleotide and 4/5 in-silico tools predict this variant to be damaging. This variant is found in 1/119558 control chromosomes from the large and broad populations of ExAC at a frequency of 0.0000084, which does not exceed the estimated maximal expected frequency of a pathogenic allele (0.0129603) in this gene. This variant has been reported in patients with CF (n=2) as well as CFTR-related phenotypes such as pancreatitis (n=1) and bronchiectasis (n=1) without strong evidence for or against pathogenicity. In one CF patient, it was reported in compound heterozygosity with another truncating variant; however, it is not specified whether such zygosity was confirmed by parental testing (Wong_2001/Sickkids db). Although this mutant showed a significantly reduced maturation, iodide transport measured in COS-7 cells were not consistent of this mutant as being a CF-causing mutation (Caputo_2009, Okiyoneda_2013). Another missense change at a nearby residue, p.Gly178Arg is reported to be causative for CF by CFTR2 database with consistent clinical and functional findings (PMID: 23974870). Taken together, although available data hints towards a possible pathogenicity, patient data are not sufficient to confirm this; therefore, it has currently been classified as a Variant of Uncertain Significance.
Counsyl RCV000577726 SCV000796468 uncertain significance Cystic fibrosis 2017-12-14 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577726 SCV000679158 not provided Cystic fibrosis no assertion provided literature only
Natera Inc RCV001027889 SCV001190611 likely pathogenic CFTR-related disorders 2019-05-20 no assertion criteria provided curation

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