ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1520C>T (p.Ser507Leu) (rs201584731)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039109 SCV000062791 uncertain significance not specified 2011-12-07 criteria provided, single submitter clinical testing The Ser507Leu variant in CDH23 has not been reported in the literature nor previ ously identified by our laboratory. This residue is conserved across species and computational analyses (biochemical amino acid properties, homology, PolyPhen2, SIFT, AlignGVGD) suggest that the Ser507Leu variant may impact the protein. How ever, this information is not predictive enough to assume pathogenicity. In summ ary, the clinical significance of this variant cannot be determined with certain ty at this time. It should be noted that this lab has only sequenced a limited number of Turkish probands and no Turkish healthy controls. In addition, healthy control information is limited in either public databases or scientific literat ure, such that the full spectrum of benign variation has not yet been defined fo r this population. Future analysis could reveal that the Ser507Leu variant is co mmon in this population and therefore unlikely to be pathogenic.
Invitae RCV001248758 SCV001422267 uncertain significance not provided 2019-10-14 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 507 of the CDH23 protein (p.Ser507Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs201584731, ExAC 0.03%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 45876). 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 C15"). 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 RCV001248758 SCV001794781 uncertain significance not provided 2020-10-29 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
Natera, Inc. RCV001275927 SCV001461607 uncertain significance Usher syndrome type 1 2020-01-24 no assertion criteria provided clinical testing

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