ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.10018C>T (p.Leu3340Phe)

gnomAD frequency: 0.00002  dbSNP: rs376537401
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Total submissions: 3
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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 RCV000155060 SCV000204744 uncertain significance not specified 2014-05-16 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Leu3340Phe vari ant in CDH23 has not been reported in individuals with hearing loss, but has bee n identified in 0.01% (1/8436) of European American chromosomes by the NHLBI Exo me Sequencing Project (http://evs.gs.washington.edu/EVS/). The amino acid (Leu) at position 3340 is not conserved in mammals or evolutionary distant species, ra ising the possibility that a change at this position may be tolerated. Additiona l computational prediction tools suggest that the Leu3340Phe variant may not imp act the protein, though this information is not predictive enough to rule out pa thogenicity. In summary, while the clinical significance of the Leu3340Phe varia nt it is uncertain, the conservation data suggests that it is more likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850122 SCV002206201 uncertain significance not provided 2022-02-09 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 3340 of the CDH23 protein (p.Leu3340Phe). This variant is present in population databases (rs376537401, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 178316). 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.
Natera, Inc. RCV001826834 SCV002086886 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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