ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1581G>T (p.Gln527His) (rs552906420)

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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 RCV000612548 SCV000712123 uncertain significance not specified 2016-06-20 criteria provided, single submitter clinical testing The p.Gln527His variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome. This variant has been identified in 4/5525 2 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs552906420). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic r ole. Computational prediction tools and conservation analyses do not provide str ong support for or against an impact to the protein. In summary, the clinical si gnificance of the p.Gln527His variant is uncertain.
Invitae RCV001243249 SCV001416395 uncertain significance not provided 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 527 of the CDH23 protein (p.Gln527His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs552906420, ExAC 0.01%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 505043). 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.

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