Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000039299 | SCV000062983 | uncertain significance | not specified | 2019-06-26 | criteria provided, single submitter | clinical testing | The p.Arg3His variant in CDH23 has been previously reported by our laboratory with one individual with hearing loss and delayed walking. This individual also harbored a second variant of uncertain significance in CDH23, but testing of parents to determine phasing was not performed. The p.Arg3His variant has been identified 0.02% (6/23796) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3. |
Invitae | RCV001248760 | SCV001422269 | uncertain significance | not provided | 2022-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3 of the CDH23 protein (p.Arg3His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 46063). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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. |
Natera, |
RCV001831680 | SCV002086114 | uncertain significance | Usher syndrome type 1 | 2019-10-28 | no assertion criteria provided | clinical testing |