Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150306 | SCV000197381 | uncertain significance | not specified | 2018-07-25 | criteria provided, single submitter | clinical testing | The p.Ala2031Thr variant in CDH23 has been previously reported by our laboratory in one individual with severe sensorineural hearing loss; however, the hearing loss was likely due to a homozygous pathogenic variant in a different gene in th is individual. It has been identified in 0.01% (15/110508) of European chromosom es by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs368381520). This variant has also been reported in ClinVar (Variation I D 162926). Computational prediction tools and conservation analysis suggest that the p.Ala2031Thr variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical signific ance of the p.Ala2031Thr variant is uncertain. ACMG/AMP Criteria applied: PP3, P M2_Supporting. |
ARUP Laboratories, |
RCV000150306 | SCV000602957 | uncertain significance | not specified | 2017-02-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001850039 | SCV002294302 | uncertain significance | not provided | 2024-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2031 of the CDH23 protein (p.Ala2031Thr). This variant is present in population databases (rs368381520, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 162926). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CDH23 protein function with a negative predictive value of 95%. 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. |
Ambry Genetics | RCV003278670 | SCV004005893 | uncertain significance | Inborn genetic diseases | 2023-04-18 | criteria provided, single submitter | clinical testing | The c.6091G>A (p.A2031T) alteration is located in exon 47 (coding exon 46) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 6091, causing the alanine (A) at amino acid position 2031 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001274899 | SCV001459452 | uncertain significance | Usher syndrome type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |