ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3118G>T (p.Asp1040Tyr)

gnomAD frequency: 0.00025  dbSNP: rs200177873
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000213719 SCV000271555 uncertain significance not specified 2015-07-02 criteria provided, single submitter clinical testing The p.Asp1040Tyr variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 16/65892 Europ ean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs200177873). Computational prediction tools and conservation a nalyses suggest that the p.Asp1040Tyr variant may impact the protein, though thi s information is not predictive enough to determine pathogenicity. In summary, t he clinical significance of the p.Asp1040Tyr variant is uncertain.
Illumina Laboratory Services, Illumina RCV000300671 SCV000363681 uncertain significance CDH23-Related Disorders 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000353250 SCV000363682 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 Laboratory Services, Illumina RCV000395353 SCV000363683 uncertain significance Autosomal recessive nonsyndromic hearing loss 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.
Invitae RCV001061643 SCV001226392 uncertain significance not provided 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1040 of the CDH23 protein (p.Asp1040Tyr). This variant is present in population databases (rs200177873, gnomAD 0.02%). 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: 228489). 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. 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.
GeneDx RCV001061643 SCV001785759 uncertain significance not provided 2021-11-05 criteria provided, single submitter clinical testing Observed in a patient with posterior uveitis in published literature; no specific patient information is available (Li et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32707200)
Fulgent Genetics, Fulgent Genetics RCV002503851 SCV002815441 uncertain significance Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2021-11-17 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001061643 SCV004033049 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing CDH23: PM2, PP3
Natera, Inc. RCV001272553 SCV001454645 uncertain significance Usher syndrome type 1 2019-11-11 no assertion criteria provided clinical testing

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