ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.325G>A (p.Asp109Asn) (rs199793172)

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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, Partners HealthCare Personalized Medicine RCV000150269 SCV000197283 uncertain significance not specified 2014-10-19 criteria provided, single submitter clinical testing The p.Asp109Asn variant in CDH23 gene has not been previously reported in indivi duals with hearing loss or in large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protei n, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Asp109Asn variant is uncertain.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755907 SCV000883557 uncertain significance not provided 2017-07-31 criteria provided, single submitter clinical testing The p.Asp109Asn variant (rs199793172) has not been reported in the medical literature; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 162865). It is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.006% (identified in 18 out of 277,142 chromosomes). The aspartic at codon 109 is moderately conserved considering 12 species (Alamut software v2.9), and computational analyses suggest this variant has a significant effect on CDH23 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Asp109Asn variant cannot be determined with certainty.
Invitae RCV000755907 SCV001417584 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 109 of the CDH23 protein (p.Asp109Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs199793172, ExAC 0.02%). This variant has not been reported in the literature in individuals with CDH23-related disease. ClinVar contains an entry for this variant (Variation ID: 162865). 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 C0"). 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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