Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |