ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.451C>A (p.Gln151Lys) (rs397508720)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047142 SCV000075155 uncertain significance Cystic fibrosis 2016-05-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 151 of the CFTR protein (p.Gln151Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs397508720, ExAC 0.006%). This variant has been reported to be correlated with congenital absence of vas deferens (PMID: 26277102). No additional clinical or genetic details were provided. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The lysine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and reported to correlate with disease, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000734737 SCV000862902 uncertain significance not provided 2018-08-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781280 SCV000919193 uncertain significance not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: CFTR c.451C>A (p.Gln151Lys) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.4e-05 in 116608 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Congenital Bilateral Absence of the Vas Deferens (3.4e-05 vs 0.013), allowing no conclusion about variant significance. c.451C>A has been reported in the literature in one individual affected with Congenital Absence of the Vas Deferens. These data do not allow any conclusion about variant significance. 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 after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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