Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156273 | SCV000205990 | uncertain significance | not specified | 2013-12-23 | criteria provided, single submitter | clinical testing | The Gly2123Arg variant in CDH23 has not been previously reported in individuals with hearing loss or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugge st that the Gly2123Arg variant may impact the protein, though this information i s not predictive enough to determine pathogenicity. In summary, additional data is needed to determine the clinical significance of this variant. |
Invitae | RCV001303575 | SCV001492824 | uncertain significance | not provided | 2021-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2123 of the CDH23 protein (p.Gly2123Arg). This variant is present in population databases (rs727504894, gnomAD 0.006%). 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: 179483). 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 C65"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Natera, |
RCV001274902 | SCV001459455 | uncertain significance | Usher syndrome type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |