Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001243516 | SCV001416684 | uncertain significance | not provided | 2024-05-23 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 589 of the CDH23 protein (p.Asp589Val). This variant is present in population databases (rs753165881, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of Usher syndrome and/or deafness (Invitae). ClinVar contains an entry for this variant (Variation ID: 968393). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDH23 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. |
Ambry Genetics | RCV004034752 | SCV004921978 | uncertain significance | Inborn genetic diseases | 2024-03-01 | criteria provided, single submitter | clinical testing | The c.1766A>T (p.D589V) alteration is located in exon 17 (coding exon 16) of the CDH23 gene. This alteration results from a A to T substitution at nucleotide position 1766, causing the aspartic acid (D) at amino acid position 589 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV001243516 | SCV005870474 | uncertain significance | not provided | 2024-08-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001835172 | SCV002093700 | uncertain significance | Usher syndrome type 1 | 2020-12-01 | no assertion criteria provided | clinical testing |