ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3986G>A (p.Gly1329Asp)

gnomAD frequency: 0.00026  dbSNP: rs201877610
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Total submissions: 8
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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 RCV000039168 SCV000062852 uncertain significance not specified 2016-06-02 criteria provided, single submitter clinical testing The p.Gly1329Asp variant in CDH23 has been previously reported in the heterozygo us state in 1 individual with hearing loss by our laboratory and in 1 individual with Usher syndrome (Bujakowska 2014). However, neither individual had a second variant affecting the remaining copy of CDH23 and the individual reported by Bu jakowska (2014) had an alternate explanation of the hearing loss identified. Thi s variant was also identified in 35/63866 European chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201877610). Al though this variant has been seen in the general population, its frequency is no t high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though t his information is not predictive enough to determine pathogenicity. In summar y, the clinical significance of the p.Gly1329Asp variant is uncertain.
GeneDx RCV000726811 SCV000577393 uncertain significance not provided 2023-02-10 criteria provided, single submitter clinical testing Observed in an individual with Usher syndrome type 1 in published literature who had a different genetic etiology for the phenotype (Bujakowska et al., 2014); 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: 24875298, 25468891)
Eurofins Ntd Llc (ga) RCV000726811 SCV000703221 uncertain significance not provided 2016-11-10 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764916 SCV000896079 uncertain significance Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001105664 SCV001262649 uncertain significance Usher syndrome type 1D 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001105665 SCV001262650 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000726811 SCV001419962 uncertain significance not provided 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1329 of the CDH23 protein (p.Gly1329Asp). This variant is present in population databases (rs201877610, gnomAD 0.06%). 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: 45934). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Natera, Inc. RCV001831663 SCV002090678 uncertain significance Usher syndrome type 1 2020-02-14 no assertion criteria provided clinical testing

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