ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4562A>G (p.Asn1521Ser)

gnomAD frequency: 0.00006  dbSNP: rs780987516
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814341 SCV001755128 likely pathogenic Ear malformation 2021-07-10 criteria provided, single submitter clinical testing
King Laboratory, University of Washington RCV001810087 SCV002059906 likely pathogenic Autosomal recessive nonsyndromic hearing loss 12 2020-08-01 criteria provided, single submitter research CDH23 c.4562A>G, p.N1521S alters a residue of CDH23 completely conserved in all sequenced vertebrates. The variant is homozygous in 3 Palestinian children with profound pre-lingual hearing loss (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and present in 5/280666 alleles on gnomAD, all heterozygotes.
Invitae RCV002568238 SCV003300688 pathogenic not provided 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1521 of the CDH23 protein (p.Asn1521Ser). This variant is present in population databases (rs780987516, gnomAD 0.008%). This missense change has been observed in individuals with deafness (PMID: 26445815, 30622556, 31850270, 32747562, 35440622). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1180612). 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. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003474004 SCV004210616 pathogenic Pituitary adenoma 5, multiple types 2023-09-18 criteria provided, single submitter clinical testing

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