Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001376753 | SCV001573914 | likely pathogenic | not provided | 2023-09-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1065907). This missense change has been observed in individuals with clinical features of Usher syndrome (PMID: 25404053, 27583663, 32860223; Invitae). This variant is present in population databases (rs767343063, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 291 of the CDH23 protein (p.Gly291Arg). |
| Gene |
RCV001376753 | SCV001813708 | likely pathogenic | not provided | 2023-10-26 | 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; This variant is associated with the following publications: (PMID: 36460718, 32860223, 27583663, 25404053) |
| 3billion | RCV002250754 | SCV002520976 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.95; 3Cnet: 0.98). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CDH23 related disorder (PMID: 25404053). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25404053, 27583663). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV003473894 | SCV004210609 | likely pathogenic | Pituitary adenoma 5, multiple types | 2023-09-28 | criteria provided, single submitter | clinical testing |