Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kariminejad - |
RCV001814341 | SCV001755128 | likely pathogenic | Ear malformation | 2021-07-10 | criteria provided, single submitter | clinical testing | |
King Laboratory, |
RCV001810087 | SCV002059906 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2020-08-01 | criteria provided, single submitter | research | CDH23 c.4562A>G, p.N1521S alters a residue of CDH23 completely conserved in all sequenced vertebrates. The variant is homozygous in 3 Palestinian children with profound pre-lingual hearing loss (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and present in 5/280666 alleles on gnomAD, all heterozygotes. |
Invitae | RCV002568238 | SCV003300688 | pathogenic | not provided | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1521 of the CDH23 protein (p.Asn1521Ser). This variant is present in population databases (rs780987516, gnomAD 0.008%). This missense change has been observed in individuals with deafness (PMID: 26445815, 30622556, 31850270, 32747562, 35440622). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1180612). 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. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003474004 | SCV004210616 | pathogenic | Pituitary adenoma 5, multiple types | 2023-09-18 | criteria provided, single submitter | clinical testing |