ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9760G>A (p.Glu3254Lys)

gnomAD frequency: 0.00003  dbSNP: rs369713078
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002041143 SCV002309598 uncertain significance not provided 2024-02-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3254 of the CDH23 protein (p.Glu3254Lys). This variant is present in population databases (rs369713078, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 1517658). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDH23 protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV002548878 SCV003715693 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.9760G>A (p.E3254K) alteration is located in exon 70 (coding exon 69) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 9760, causing the glutamic acid (E) at amino acid position 3254 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV002041143 SCV005387041 uncertain significance not provided 2024-02-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.