ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9629T>C (p.Ile3210Thr)

gnomAD frequency: 0.00026  dbSNP: rs144688588
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Total submissions: 16
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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 RCV000155059 SCV000204743 uncertain significance not specified 2020-06-01 criteria provided, single submitter clinical testing The p.Ile3210Thr variant in CDH23 has been previously identified by our laboratory in 2 probands with hearing loss; however, a variant affecting the remaining copy of CDH23 was not identified in either proband, and an alternate explanation of the hearing loss was identified in one proband. This variant has been reported in ClinVar (Variation ID 178315), and has been identified in 0.05% (67/127654) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the p.Ile3210Thr variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, the clinical significance of the p .Ile3210Thr variant is uncertain. ACMG/AMP criteria applied: PM2_Supporting, BP4.
Illumina Laboratory Services, Illumina RCV000317072 SCV000363942 uncertain significance Retinitis pigmentosa-deafness syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV004577725 SCV000363943 uncertain significance Hearing loss, autosomal recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000298108 SCV000483095 likely benign Atypical Gaucher Disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000353393 SCV000483096 likely benign Combined PSAP deficiency 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000277348 SCV000483097 likely benign Metachromatic leukodystrophy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000313766 SCV000483098 likely benign Galactosylceramide beta-galactosidase deficiency 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001241617 SCV001414647 likely benign not provided 2024-12-16 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001526764 SCV001737320 uncertain significance Usher syndrome type 1D 2021-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001241617 SCV001812958 uncertain significance not provided 2024-01-19 criteria provided, single submitter clinical testing Identified with a second variant (phase unknown) in an individual with Usher syndrome in published literature (PMID: 23794683); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23794683)
Mayo Clinic Laboratories, Mayo Clinic RCV001241617 SCV004225275 uncertain significance not provided 2023-02-09 criteria provided, single submitter clinical testing PM2_supporting
Laboratory of Prof. Karen Avraham, Tel Aviv University RCV004821276 SCV005442582 uncertain significance Autosomal recessive nonsyndromic hearing loss 12 2024-12-25 criteria provided, single submitter research The CDH23 c.9629T>C:p.(Ile3210Thr) variant is extremely rare and predicted deleterious by all prediction programs. It was detected in an individual with sloping normal-to-severe HL, that carried another CDH23 VUS, c.7849G>C:p.(Gly2617Arg), as well as an additional pathogenic variant in another USH gene, ADGRV1, c.16640G>A:p.(Arg5547His), suggesting compound heterozygosity, or digenic inheritance, or an additive involvement of all three variants.
Natera, Inc. RCV001276933 SCV001463591 uncertain significance Usher syndrome type 1 2020-09-16 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001241617 SCV001924261 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001241617 SCV001967207 uncertain significance not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004757144 SCV005362618 uncertain significance CDH23-related disorder 2024-09-27 no assertion criteria provided clinical testing The CDH23 c.9629T>C variant is predicted to result in the amino acid substitution p.Ile3210Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.052% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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