ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5632G>A (p.Ala1878Thr) (rs757570269)

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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 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 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1878 of the CDH23 protein (p.Ala1878Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs757570269, ExAC 0.004%). This variant has not been reported in the literature in individuals 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.

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