ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4825G>A (p.Glu1609Lys)

gnomAD frequency: 0.00002  dbSNP: rs563582184
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001763142 SCV001991727 uncertain significance not provided 2019-09-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001763142 SCV003453974 uncertain significance not provided 2024-10-29 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 1609 of the CDH23 protein (p.Glu1609Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1307606). 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) has been performed 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.
Ambry Genetics RCV003163841 SCV003904362 uncertain significance Inborn genetic diseases 2023-02-22 criteria provided, single submitter clinical testing The c.4825G>A (p.E1609K) alteration is located in exon 38 (coding exon 37) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 4825, causing the glutamic acid (E) at amino acid position 1609 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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