ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1543A>G (p.Ile515Val)

gnomAD frequency: 0.00003  dbSNP: rs727504914
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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, Mass General Brigham Personalized Medicine RCV000156299 SCV000206017 likely benign not specified 2014-02-01 criteria provided, single submitter clinical testing Ile515Val in Exon 16 of CDH23: This variant is not expected to have clinical sig nificance because the isoleucine (Ile) residue at position 515 is not conserved through species, with squirrel, white rhinoceros, star nosed mole, and armadillo having a valine (Val) at this position. In addition, computational analyses (bi ochemical amino acid properties, AlignGVGD, PolyPhen2, SIFT) do not suggest an i mpact to the protein.
Athena Diagnostics Inc RCV000991773 SCV001143500 uncertain significance not provided 2019-10-25 criteria provided, single submitter clinical testing
Invitae RCV000991773 SCV003469557 uncertain significance not provided 2022-05-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 515 of the CDH23 protein (p.Ile515Val). This variant is present in population databases (rs727504914, gnomAD 0.009%). 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: 179509). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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