ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1582G>A (p.Glu528Lys) (rs773018372)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000591105 SCV000883576 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing The CFTR c.1582G>A; p.Glu528Lys variant is not published in the medical literature or in the ClinVar database. The variant is listed in a gene-specific database in one individual identified by newborn screen (see link below). The variant is listed in the dbSNP variant database (rs773018372) and in the Genome Aggregation Database with an allele frequency of 0.002 (5/245500 alleles). The glutamic acid at this position is moderately conserved across species and computational algorithms (AlignGVGD, PolyPhen2, SIFT) predict this variant is tolerated. Considering available information, the clinical significance of this variant cannot be determined with certainty. References: Link to CFTR E528K in database: http://www.genet.sickkids.on.ca/cftr/MutationDetailPage.external?sp=1653
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000591105 SCV000708622 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing
Invitae RCV000809718 SCV000949888 uncertain significance Cystic fibrosis 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 528 of the CFTR protein (p.Glu528Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs773018372, ExAC 0.01%). This variant has not been reported in the literature in individuals with CFTR-related disease. ClinVar contains an entry for this variant (Variation ID: 502030). 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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