ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7568C>T (p.Pro2523Leu)

gnomAD frequency: 0.00006  dbSNP: rs369761606
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Total submissions: 3
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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 RCV000825889 SCV000967374 uncertain significance not specified 2020-10-23 criteria provided, single submitter clinical testing The p.Pro2523Leu variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.04% (14/30602) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org/). This variant has been reported in ClinVar (Variation ID 667212). Computational prediction tools and conservation analysis suggest that the p.Pro2523Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro2523Leu variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Invitae RCV001242078 SCV001415142 uncertain significance not provided 2022-10-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2523 of the CDH23 protein (p.Pro2523Leu). This variant is present in population databases (rs369761606, gnomAD 0.05%). 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: 667212). 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.
Natera, Inc. RCV001825684 SCV002093411 uncertain significance Usher syndrome type 1 2020-02-21 no assertion criteria provided clinical testing

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