ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1637G>A (p.Arg546Gln) (rs199508694)

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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 RCV000039112 SCV000062794 uncertain significance not specified 2012-07-30 criteria provided, single submitter clinical testing The Arg546Gln variant in CDH23 has not been reported in the literature, but has now been identified in 2/36 Black or African American individuals with hearing l oss by our laboratory, neither of whom has a second CDH23 variant. In addition, this variant has been identified in 0.1% (4/4234) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS/). However, this frequency is not enough to rule out a pathoge nic role. Computational analyses (biochemical amino acid properties, conservatio n, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional data is needed to determine the clinical significance of this variant.
Invitae RCV001042981 SCV001206691 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 546 of the CDH23 protein (p.Arg546Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199508694, ExAC 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with CDH23-related disease. ClinVar contains an entry for this variant (Variation ID: 45879). 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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