ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1853A>G (p.Tyr618Cys) (rs778493031)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521699 SCV000620245 uncertain significance not provided 2017-09-06 criteria provided, single submitter clinical testing The Y618C variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y618C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The Y618C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Y618C as a variant of uncertain significance.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825300 SCV000966595 uncertain significance not specified 2019-01-04 criteria provided, single submitter clinical testing The c.Tyr618Cys variant in CDH23 has been reported by our laboratory in 1 indivi dual with progressive severe hearing loss as an assumed de novo variant. This in dividual also harbored a second variant of uncertain significance in CDH23. This variant was identified in 1/104828 European chromosomes by gnomAD (http://gnoma d.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical signific ance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM6.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000521699 SCV001246546 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing

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