ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.499G>A (p.Val167Ile) (rs772995621)

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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 RCV000603073 SCV000731999 uncertain significance not specified 2017-11-15 criteria provided, single submitter clinical testing The p.Val167Ile variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 4/126512 Europe an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs772995621). Although this variant has been seen in the gene ral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong s upport for or against an impact to the protein. In summary, the clinical signifi cance of the p.Val167Ile variant is uncertain. ACMG/AMP Criteria applied: PM2.
Invitae RCV001037297 SCV001200706 uncertain significance not provided 2019-10-10 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 167 of the CDH23 protein (p.Val167Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs772995621, ExAC 0.005%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 517628). 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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