Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001244897 | SCV001418149 | uncertain significance | not provided | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 146 of the CDH23 protein (p.Pro146Leu). 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 missense change has been observed in individual(s) with deafness (PMID: 27610647, 33924653). ClinVar contains an entry for this variant (Variation ID: 969524). 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. |
| Gene |
RCV001244897 | SCV002553057 | uncertain significance | not provided | 2022-01-02 | 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; Observed in patients with hearing loss in the published literature, although familial segregation information and additional clinical information were not included (Chen et al., 2016; Santos-Cortez et al., 2021); This variant is associated with the following publications: (PMID: 27610647, 33924653) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317466 | SCV004021189 | uncertain significance | not specified | 2023-06-01 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.437C>T (p.Pro146Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 242478 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.437C>T has been reported in the literature in at least two individuals with deafness without strong evidence for causality (e.g., Chen_2016, Santos-Cortez_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27610647, 33924653). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Natera, |
RCV001829942 | SCV002086734 | uncertain significance | Usher syndrome type 1 | 2020-06-25 | no assertion criteria provided | clinical testing |