ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.535G>A (p.Ala179Thr)

gnomAD frequency: 0.00003  dbSNP: rs371422466
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000219086 SCV000270041 likely benign not specified 2015-05-28 criteria provided, single submitter clinical testing p.Ala179Thr in exon 7 of CDH23: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of note, 6 different mammals have a threonine (Thr) at this position despite high n earby amino acid sequence conservation. In addition, computational prediction t ools do not suggest a high likelihood of impact to the protein. It has been iden tified in 2/120284 chromosomes by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org; dbSNP rs371422466).
Labcorp Genetics (formerly Invitae), Labcorp RCV001853407 SCV002145726 uncertain significance not provided 2024-08-19 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 179 of the CDH23 protein (p.Ala179Thr). This variant is present in population databases (rs371422466, gnomAD 0.007%). This missense change has been observed in individual(s) with deafness (PMID: 26445815). ClinVar contains an entry for this variant (Variation ID: 227228). 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.

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