ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.2263C>T (p.His755Tyr) (rs181255269)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001089680 SCV001245164 benign Nonsyndromic hearing loss and deafness 2020-01-15 reviewed by expert panel curation The filtering allele frequency of the c.2263C>T (p.His755Tyr) variant in CDH23 is 0.73% (248/30558) for South Asian chromosomes by gnomAD v2.1.1, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). Of note, this variant was reported in 2 individuals with Usher syndrome, though without any evidence of pathogenicity (PM3 not met; PMID: 18429043, 21569298). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel (BA1).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039124 SCV000062806 benign not specified 2015-12-17 criteria provided, single submitter clinical testing p.His755Tyr in exon 21 of CDH23: This variant is not expected to have clinical s ignificance because it has been identified in 0.85% (136/16100) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs181255269).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000039124 SCV000202374 likely benign not specified 2016-08-30 criteria provided, single submitter clinical testing
GeneDx RCV000487684 SCV000568533 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing The H755Y variant in the CDH23 gene has been reported previously in a few individuals with Usher syndrome; however, additional clinical and familial segregation information were not included in these reports (Oshima et al., 2008; Bonnet et al., 2011). In addition, the H755Y variant was observed in an consanguineous family with Usher syndrome type 2, where a USH2A nonsense variant was found to co-segregate with disease in homozygous individuals (Le Quesne Stabej et al., 2012). The H755Y variant is observed in 250/30,740 (0.81%) alleles from individuals of South Asian background, including one homozygous individual, in large population cohorts (Lek et al., 2016). The H755Y variant 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. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret H755Y as a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487684 SCV000574842 uncertain significance not provided 2019-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515411 SCV000611446 uncertain significance Deafness, autosomal recessive 12; Usher syndrome type 1D 2017-05-23 criteria provided, single submitter clinical testing
Invitae RCV000487684 SCV001101191 likely benign not provided 2020-12-08 criteria provided, single submitter clinical testing
Mendelics RCV000988379 SCV001138073 uncertain significance Retinitis pigmentosa-deafness syndrome 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001331230 SCV001523223 uncertain significance Deafness, autosomal recessive 12 2019-09-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Nilou-Genome Lab RCV001526743 SCV001737213 benign Usher syndrome type 1D 2021-05-18 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001331230 SCV001750473 benign Deafness, autosomal recessive 12 2021-07-01 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787557 SCV000926532 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001034601 SCV001197981 likely benign Non-Syndromic Hereditary Hearing Impairment no assertion criteria provided research
Natera, Inc. RCV001275939 SCV001461619 uncertain significance Usher syndrome type 1 2020-04-15 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000487684 SCV001800283 likely benign not provided no assertion criteria provided clinical testing

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.