ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3712T>G (p.Ser1238Ala)

dbSNP: rs764805425
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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 RCV000825888 SCV000967373 uncertain significance not specified 2018-06-21 criteria provided, single submitter clinical testing The p.Ser1238Ala variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome but has been identified in 2/111506 Europe an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs764805425). Computational prediction tools and conservation analysis suggest that the p.Ser1238Ala variant may not impact the protein, thou gh this information is not predictive enough to rule out pathogenicity. In summa ry, the clinical significance of the p.Ser1238Ala variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV001371495 SCV001568062 uncertain significance not provided 2025-01-02 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1238 of the CDH23 protein (p.Ser1238Ala). This variant is present in population databases (rs764805425, gnomAD 0.002%). 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: 667211). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. RCV001830843 SCV002090600 uncertain significance Usher syndrome type 1 2020-11-11 no assertion criteria provided clinical testing

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