ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7568C>T (p.Pro2523Leu) (rs369761606)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825889 SCV000967374 uncertain significance not specified 2018-08-01 criteria provided, single submitter clinical testing The p.Pro2523Leu variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 0.04% (15/3078 2) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org/). Computational prediction tools and conservation an alysis suggest that the p.Pro2523Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, th e clinical significance of the p.Pro2523Leu variant is uncertain. ACMG/AMP Crite ria applied: PM2_Supporting, PP3.
Invitae RCV001242078 SCV001415142 uncertain significance not provided 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2523 of the CDH23 protein (p.Pro2523Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs369761606, ExAC 0.05%). This variant has not been reported in the literature in individuals with CDH23-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.

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