ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4045G>A (p.Gly1349Ser) (rs201686600)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000295222 SCV000344301 uncertain significance not provided 2017-06-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780113 SCV000917157 uncertain significance not specified 2018-01-24 criteria provided, single submitter clinical testing Variant summary: The CFTR c.4045G>A (p.Gly1349Ser) variant located in the nucleotide-binding fold (via Wilkinson_1996)) involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome for this variant. A functional study, Wilkinson_1996, found that the variant slowed the rate of approach to steady state activation. This variant was found in 4/246022 control chromosomes (gnomAD and publication controls), predominantly observed in the East Asian subpopulation at a frequency of 0.000232 (4/17234). This frequency does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant. A publication, Anazi_2003, reports a CBAVD pt that was a compound heterozygote, G1349S/Q1352H (possibly pathogenic in our internal database). A clinical diagnostic laboratory classifies the variant as "uncertain significance." Another variant, c.4046G>A causing a missense change at this codon, Gly1349Asp, has been reported as "likely pathogenic/pathogenic," via ClinVar, further supporting the importance of this location in CFTR protein function. Taken together, this variant is classified as a "Variant of Uncertain Significance - Possibly Pathogenic."

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.