ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.8533C>T (p.Arg2845Cys) (rs727505254)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156776 SCV000206497 uncertain significance not specified 2014-09-09 criteria provided, single submitter clinical testing The Arg2845Cys variant in CDH23 has not been previously reported in individuals with hearing loss or in large population studies. Computational prediction tool s and conservation analyses do not provide strong support for or against an impa ct to the protein. In summary, the clinical significance of the Arg2845Cys varia nt is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV000365153 SCV000363891 uncertain significance Usher syndrome type 1D 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000394912 SCV000363892 uncertain significance Deafness, autosomal recessive 12 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000302373 SCV000363893 uncertain significance CDH23-Related Disorders 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000757071 SCV000535135 uncertain significance not provided 2018-03-05 criteria provided, single submitter clinical testing The R2845C variant in the CDH23 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R2845C is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757071 SCV000885162 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing The p.Arg2845Cys variant (rs727505254) has not been reported in the medical literature, nor has it been previously identified in our laboratory. The p.Arg2845Cys variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.005% (identified in 13 out of 263,592 chromosomes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 179973). The arginine at codon 2845 is highly conserved considering 12 species up to zebrafish (Alamut software v2.10.0), and computational analyses suggest that this variant affects the structure/function of the CDH23 protein (SIFT: damaging, PolyPhen2: possibly damaging, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.Arg2845Cys variant cannot be determined with certainty.

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.