ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.1037C>T (p.Pro346Leu)

gnomAD frequency: 0.00002  dbSNP: rs778251205
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001203945 SCV001375130 pathogenic not provided 2023-03-16 criteria provided, single submitter clinical testing 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 expected to disrupt CDH23 protein function. ClinVar contains an entry for this variant (Variation ID: 402251). This missense change has been observed in individual(s) with hearing loss (PMID: 19888295). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs778251205, gnomAD 0.008%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 346 of the CDH23 protein (p.Pro346Leu). This variant disrupts the p.Arg346 amino acid residue in CDH23. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19888295). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
King Laboratory, University of Washington RCV000454126 SCV002059903 likely pathogenic Autosomal recessive nonsyndromic hearing loss 12 2020-08-01 criteria provided, single submitter research CDH23 c.1037C>T, p.P346L alters a highly conserved residue of CDH23. The variant is homozygous in 3 Palestinian children with pre-lingual moderate hearing loss (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and present in 5/280726 alleles on gnomAD, all heterozygotes.
Hereditary Research Laboratory, Bethlehem University RCV000454126 SCV000538087 pathogenic Autosomal recessive nonsyndromic hearing loss 12 2016-06-04 no assertion criteria provided research

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