Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
King Laboratory, |
RCV000454137 | SCV002059907 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2020-08-01 | criteria provided, single submitter | research | CDH23 c.5749G>A, p.E1917K alters a residue of CDH23 in the Usher1D domain that is completely conserved in all sequenced vertebrates. The variant is homozygous in 3 Palestinian individuals with profound pre-lingual hearing loss and retinitis pigmentosa (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and from gnomAD v2.1.1. |
Invitae | RCV002522743 | SCV003463336 | pathogenic | not provided | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1917 of the CDH23 protein (p.Glu1917Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with bilateral deafness and/or clinical features of Usher syndrome (PMID: 29889784, 32747562). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 402248). 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 expected to disrupt CDH23 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003476019 | SCV004210644 | likely pathogenic | Pituitary adenoma 5, multiple types | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Hereditary Research Laboratory, |
RCV000454137 | SCV000538084 | pathogenic | Autosomal recessive nonsyndromic hearing loss 12 | 2016-06-04 | no assertion criteria provided | research | HL and (in one branch) RP and epilepsy |