ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1581G>T (p.Gln527His)

gnomAD frequency: 0.00016  dbSNP: rs552906420
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Total submissions: 5
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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 RCV000612548 SCV000712123 uncertain significance not specified 2016-06-20 criteria provided, single submitter clinical testing The p.Gln527His variant in CDH23 has not been previously reported in individuals with hearing loss or Usher syndrome. This variant has been identified in 4/5525 2 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs552906420). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic r ole. Computational prediction tools and conservation analyses do not provide str ong support for or against an impact to the protein. In summary, the clinical si gnificance of the p.Gln527His variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001243249 SCV001416395 uncertain significance not provided 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 527 of the CDH23 protein (p.Gln527His). This variant is present in population databases (rs552906420, 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: 505043). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
GeneDx RCV001243249 SCV002102672 uncertain significance not provided 2022-03-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003362855 SCV004056650 uncertain significance Inborn genetic diseases 2023-06-23 criteria provided, single submitter clinical testing The c.1581G>T (p.Q527H) alteration is located in exon 16 (coding exon 15) of the CDH23 gene. This alteration results from a G to T substitution at nucleotide position 1581, causing the glutamine (Q) at amino acid position 527 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001829701 SCV002091241 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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