ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9413G>A (p.Arg3138Gln) (rs372676235)

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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 RCV000213318 SCV000271575 uncertain significance not specified 2015-08-11 criteria provided, single submitter clinical testing The p.Arg3183Gln variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 12/16510 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi; dbSNP rs372676235). Although this variant has been seen in the gen eral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that this vari ant may impact the protein. Additional computational tools also suggested an im pact to splicing. However, this information is not predictive enough to determi ne pathogenicity or a splicing impact. In summary, the clinical significance of the p.Arg3183Gln variant is uncertain.
Invitae RCV001062127 SCV001226906 uncertain significance not provided 2020-01-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3138 of the CDH23 protein (p.Arg3138Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs372676235, ExAC 0.07%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 228508). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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