ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7361C>T (p.Thr2454Met)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195486 SCV001365863 uncertain significance not specified 2019-05-22 criteria provided, single submitter clinical testing The p.Thr2454Met variant in CDH23 has been previously identified in 1 patient with hearing loss who harbored another CDH23 variant in trans (Jung 2017). The p.Thr2454Met variant has been identified in 0.03% (10/30602) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PM2_Supporting, PP3, PM3_Supporting.
Invitae RCV001243656 SCV001416828 uncertain significance not provided 2019-10-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 2454 of the CDH23 protein (p.Thr2454Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs772949926, ExAC 0.03%). This variant has been observed in an individual affected with hearing loss (PMID: 28383030). 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 C65"). 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.

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