ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1867G>A (p.Val623Ile) (rs143782870)

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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 RCV000155045 SCV000204729 uncertain significance not specified 2018-02-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Val623Ile var iant in CDH23 has been previously reported by our laboratory in the homozygous s tate in 1 individual with hearing loss with delayed walking; however, this patie nt harbored a homozygous likely pathogenic variant in another gene that explaine d the phenotype. This variant has also been identified in 0.13% (39/29954) of So uth Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad. broadinstitute.org/; dbSNP rs143782870); however its frequency is not high enoug h to rule out a pathogenic role. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Val623Ile variant is uncer tain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_P, BP5.
Invitae RCV001060903 SCV001225623 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 623 of the CDH23 protein (p.Val623Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs143782870, ExAC 0.2%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 178301). 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 C25"). 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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