ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9566G>A (p.Arg3189Gln) (rs727502936)

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
ClinGen Hearing Loss Variant Curation Expert Panel RCV000787977 SCV000927000 uncertain significance Usher syndrome 2019-04-29 reviewed by expert panel curation The c.9566G>A (p.Arg3189Gln) variant in CDH23 has been identified in 1 heterozygous patient with sensorineural hearing loss (Partners LMM internal data, SCV000197429.4). The allele frequency of the variant is 0.023% (7/30608) of South Asian chromosomes by gnomAD, which is a low enough frequency to apply PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : PM2_Supporting.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150330 SCV000197429 uncertain significance not specified 2014-03-15 criteria provided, single submitter clinical testing The Arg3189Gln variant in CDH23 has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational pr ediction tools and conservation analyses do not provide strong support for or ag ainst an impact to the protein. In summary, additional information is needed to determine the clinical significance of this variant.
Invitae RCV001064686 SCV001229599 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3189 of the CDH23 protein (p.Arg3189Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs727502936, ExAC 0.01%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 162956). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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.