ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3133G>T (p.Val1045Leu) (rs377100683)

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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 RCV000039143 SCV000062827 uncertain significance not specified 2013-02-22 criteria provided, single submitter clinical testing The Val1045Leu variant in CDH23 has not been reported in the literature nor prev iously identified by our laboratory. This variant has been identified in 0.05% ( 2/4268) of African American chromosomes in a broad population by the NHLBI Exome sequencing project ( Although this variant h as been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational analyses (biochemical amino acid propertie s, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support f or or against an impact to the protein. In summary, additional data is needed to determine the clinical significance of this variant.
Invitae RCV001243389 SCV001416545 uncertain significance not provided 2019-09-23 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1045 of the CDH23 protein (p.Val1045Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs377100683, ExAC 0.07%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 45910). 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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