ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4582G>A (p.Glu1528Lys) (rs201533282)

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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 RCV000825882 SCV000967367 uncertain significance not specified 2018-03-21 criteria provided, single submitter clinical testing The p.Glu1528Lys variant in CDH23 has not been previously reported in individual s hearing loss or Usher syndrome, but has been identified in 0.02% (26/126708) E uropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs149752120). 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 analysis suggest that the p .Glu1528Lys variant may not impact the protein, though this information is not p redictive enough to rule out pathogenicity. In summary, the clinical significanc e of the p.Glu1528Lys variant is uncertain. ACMG/AMP Criteria applied: BP4.
Invitae RCV001050380 SCV001214483 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1528 of the CDH23 protein (p.Glu1528Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs201533282, ExAC 0.02%). This variant has not been reported in the literature in individuals with CDH23-related conditions. 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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