ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.499G>A (p.Val167Ile)

gnomAD frequency: 0.00004  dbSNP: rs772995621
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Total submissions: 4
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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 RCV000603073 SCV000731999 uncertain significance not specified 2017-11-15 criteria provided, single submitter clinical testing The p.Val167Ile variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 4/126512 Europe an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs772995621). Although this variant has been seen in the gene ral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong s upport for or against an impact to the protein. In summary, the clinical signifi cance of the p.Val167Ile variant is uncertain. ACMG/AMP Criteria applied: PM2.
Labcorp Genetics (formerly Invitae), Labcorp RCV001037297 SCV001200706 uncertain significance not provided 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 167 of the CDH23 protein (p.Val167Ile). This variant is present in population databases (rs772995621, gnomAD 0.006%). 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: 517628). 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 RCV002528794 SCV003740328 uncertain significance Inborn genetic diseases 2022-04-25 criteria provided, single submitter clinical testing The c.499G>A (p.V167I) alteration is located in exon 7 (coding exon 6) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the valine (V) at amino acid position 167 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275414 SCV001460564 uncertain significance Usher syndrome type 1 2020-04-11 no assertion criteria provided clinical testing

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