ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9883A>C (p.Thr3295Pro)

gnomAD frequency: 0.00006  dbSNP: rs781716568
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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 RCV000213175 SCV000271578 uncertain significance not specified 2015-01-30 criteria provided, single submitter clinical testing The p.Thr3295Pro variant in CDH23 has not been previously reported in individual s with hearing loss, but has been identified in 3/10434 of Latino chromosomes an d 1/58040 European chromosomes by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org; dbSNP rs368112637). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr3295Pro variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001052960 SCV001217197 uncertain significance not provided 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 3295 of the CDH23 protein (p.Thr3295Pro). This variant is present in population databases (rs781716568, 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: 228511). 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 RCV001052960 SCV002588049 uncertain significance not provided 2022-10-19 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
Ambry Genetics RCV002519625 SCV003686564 uncertain significance Inborn genetic diseases 2022-11-18 criteria provided, single submitter clinical testing The c.9883A>C (p.T3295P) alteration is located in exon 70 (coding exon 69) of the CDH23 gene. This alteration results from a A to C substitution at nucleotide position 9883, causing the threonine (T) at amino acid position 3295 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001828069 SCV002086386 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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