ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7177G>A (p.Val2393Met)

gnomAD frequency: 0.00002  dbSNP: rs775436759
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Total submissions: 5
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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 RCV000609825 SCV000712120 uncertain significance not specified 2016-06-02 criteria provided, single submitter clinical testing The p.Val2393Met variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 3/8624 East As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs775436759). Although this variant has been seen in the gener al population, its frequency is not high enough to rule out a pathogenic role. C omputational prediction tools and conservation analysis do not provide strong su pport for or against an impact to the protein. In summary, the clinical signific ance of this variant is uncertain.
Invitae RCV001860242 SCV002205137 uncertain significance not provided 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2393 of the CDH23 protein (p.Val2393Met). This variant is present in population databases (rs775436759, gnomAD 0.03%). 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: 505041). 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.
Fulgent Genetics, Fulgent Genetics RCV002498890 SCV002797580 uncertain significance Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2021-07-30 criteria provided, single submitter clinical testing
GeneDx RCV001860242 SCV003924779 uncertain significance not provided 2022-11-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28539123)
Natera, Inc. RCV001834922 SCV002093322 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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