ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5168G>A (p.Arg1723His) (rs189361642)

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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 RCV000150298 SCV000197361 uncertain significance not specified 2015-08-18 criteria provided, single submitter clinical testing The p.Arg1723His variant in CDH23 has been previously reported in the heterozygo us state in one individual with hearing loss, but a second variant affecting the other copy of the gene was not found. It has also been identified in 4/66584 Eu ropean chromosomes and 2/9754 African chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs189361642). Although this v ariant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this informati on is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1723His variant is uncertain.
Invitae RCV001248348 SCV001421824 uncertain significance not provided 2019-09-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1723 of the CDH23 protein (p.Arg1723His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs189361642, ExAC 0.02%). This variant has not been reported in the literature in individuals with CDH23-related disease. ClinVar contains an entry for this variant (Variation ID: 162919). 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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