ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.10007C>T (p.Pro3336Leu)

gnomAD frequency: 0.00003  dbSNP: rs727504532
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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 RCV000155682 SCV000205392 uncertain significance not specified 2013-11-26 criteria provided, single submitter clinical testing The Pro3336Leu variant in CDH23 has not been previously reported in individuals with hearing loss. Frequency data from large population studies is insufficient. Computational analyses (biochemical amino acid properties, conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the Pro3336Leu variant may impact the pro tein, though this information is not predictive enough to determine pathogenicit y. In summary, additional data is needed to determine the clinical significance of this variant.
Invitae RCV001857533 SCV002311283 uncertain significance not provided 2021-09-09 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 3336 of the CDH23 protein (p.Pro3336Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). 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: 178909). 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.
Natera, Inc. RCV001826840 SCV002086875 uncertain significance Usher syndrome type 1 2020-09-25 no assertion criteria provided clinical testing

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