ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9979G>A (p.Ala3327Thr)

gnomAD frequency: 0.00006  dbSNP: rs200733236
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825883 SCV000967368 uncertain significance not specified 2018-10-04 criteria provided, single submitter clinical testing The p.Ala3327Thr variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 0.018% (23/123 684) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Compu tational prediction tools and conservation analysis suggest that this variant ma y impact the protein, though this information is not predictive enough to determ ine pathogenicity. In summary, the clinical significance of this variant is unce rtain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Invitae RCV002538230 SCV003454011 uncertain significance not provided 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3327 of the CDH23 protein (p.Ala3327Thr). This variant is present in population databases (rs200733236, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 667206). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDH23 protein function. 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.
Natera, Inc. RCV001271958 SCV001453533 uncertain significance Usher syndrome type 1 2020-09-16 no assertion criteria provided clinical testing

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