ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.553G>A (p.Gly185Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion, Medical Genetics RCV002283694 SCV002572680 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). While this variant results in missense change, protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 0.77). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Institute of Rare Diseases, West China Hospital, Sichuan University RCV002283694 SCV005687009 likely pathogenic Autosomal recessive nonsyndromic hearing loss 12 2025-01-09 criteria provided, single submitter research PM3_Strong;PM2_Supporting;PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV005096036 SCV005824372 uncertain significance not provided 2024-05-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 185 of the CDH23 protein (p.Gly185Ser). This variant is present in population databases (rs375465342, gnomAD 0.007%). 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: 1705380). 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. 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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