Description
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1701 of the CDH23 protein (p.Glu1701Lys). This variant is present in population databases (rs764025875, gnomAD 0.01%). This missense change has been observed in individuals with deafness (PMID: 24416283, 29287849). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2136884). 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%. 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.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |