ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.8225C>T (p.Pro2742Leu) (rs758360283)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725749 SCV000339142 uncertain significance not provided 2016-02-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000391826 SCV000731743 uncertain significance not specified 2017-07-11 criteria provided, single submitter clinical testing The p.Pro2742Leu variant in CDH23 has not been previously reported in individual s with hearing loss. It has been reported in an individual with unspecified affe cted status in ClinVar (Variation ID 285919) as of uncertain significance. It ha s also been identified in 9/126192 European chromosomes by the Genome Aggregatio n Database (gnomAD,; dbSNP rs758360283). Althou gh this variant has been seen in the general population, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro2742Leu variant is un certain.
Invitae RCV000725749 SCV001222435 uncertain significance not provided 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2742 of the CDH23 protein (p.Pro2742Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs758360283, ExAC 0.006%). This variant has not been reported in the literature in individuals with CDH23-related disease. ClinVar contains an entry for this variant (Variation ID: 285919). 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: "Tolerated"; 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.
GeneDx RCV000725749 SCV001773109 uncertain significance not provided 2019-08-14 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001276045 SCV001461873 uncertain significance Usher syndrome type 1 2020-01-24 no assertion criteria provided clinical testing

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