ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5632G>A (p.Ala1878Thr)

gnomAD frequency: 0.00002  dbSNP: rs757570269
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Total submissions: 4
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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 RCV000606077 SCV000731776 uncertain significance not specified 2017-07-13 criteria provided, single submitter clinical testing The p.Ala1878Thr variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 5/111700 Europ ean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org/; dbSNP rs757570269). Although this variant has been seen in the ge neral population, its frequency is not high enough to rule out a pathogenic role . Computational prediction tools and conservation analysis suggest that the vari ant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Ala1878T hr variant is uncertain.
Invitae RCV001045655 SCV001209520 uncertain significance not provided 2022-07-12 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 1878 of the CDH23 protein (p.Ala1878Thr). This variant is present in population databases (rs757570269, gnomAD 0.004%). 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: 517480). 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 C55"). 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.
GeneDx RCV001045655 SCV002061079 uncertain significance not provided 2022-01-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15537665)
Natera, Inc. RCV001829730 SCV002092432 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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