ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.9629T>C (p.Ile3210Thr) (rs144688588)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare 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 Clinical Services Laboratory,Illumina RCV000317072 SCV000363942 uncertain significance Retinitis pigmentosa-deafness syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000371681 SCV000363943 uncertain significance Nonsyndromic Hearing Loss, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000298108 SCV000483095 likely benign Atypical Gaucher Disease 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000353393 SCV000483096 likely benign Combined saposin deficiency 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000277348 SCV000483097 likely benign Metachromatic leukodystrophy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313766 SCV000483098 likely benign Galactosylceramide beta-galactosidase deficiency 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001241617 SCV001414647 uncertain significance not provided 2019-11-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3210 of the CDH23 protein (p.Ile3210Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs144688588, ExAC 0.07%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 178315). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.
Nilou-Genome 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 2021-05-17 criteria provided, single submitter clinical testing Identified with a second CDH23 variant, phase unknown, in an individual with Usher syndrome (Selcen et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23794683)
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

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