ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.2330C>A (p.Thr777Lys) (rs199709482)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039127 SCV000062809 uncertain significance not specified 2013-02-14 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Thr777Lys varia nt in CDH23 has not been reported in the literature nor previously identified by our laboratory. Computational analyses (biochemical amino acid properties, cons ervation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or a gainst an impact to the protein. This variant has been identified in 0.1% (3/418 2) of African American chromosomes in a broad population by the NHLBI Exome sequ encing project (http://evs.gs.washington.edu/EVS/). Although this variant has be en seen in the general population, its frequency is not high enough to rule out a pathogenic role. Additional information is needed to fully assess the clinical significance of the Thr777Lys variant.
GeneDx RCV000658191 SCV000779962 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing The T777K variant in the CDH23 gene has been reported previously with a second CDH23 variant in a patient with Usher syndrome type 1, however, additional clinical and familial segregation information was not included (Bonnet et al., 2016). The T777K variant is observed in 5/30,782 (0.016%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The T777K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret T777K 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.