ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7615G>C (p.Gly2539Arg)

gnomAD frequency: 0.00004  dbSNP: rs373649718
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Total submissions: 4
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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 RCV000039271 SCV000062955 uncertain significance not specified 2012-08-28 criteria provided, single submitter clinical testing The Gly2539Arg variant in CDH23 has not been reported in the literature nor prev iously identified by our laboratory. This variant has been identified in 1/8346 (0.01%) European American chromosomes from a broad, though clinically unspecifie d population (NHLBI Exome Sequencing Project; http://evs.gs.washington.edu/EVS). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational analyses (biochemi cal amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Gly2539Arg variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, additional data is needed to determine the clinical significance of this variant.
Invitae RCV002513533 SCV003522128 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2539 of the CDH23 protein (p.Gly2539Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs373649718, ExAC 0.009%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 46035). 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 C15"). 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.
Ambry Genetics RCV002513534 SCV003545154 uncertain significance Inborn genetic diseases 2021-10-05 criteria provided, single submitter clinical testing The c.7615G>C (p.G2539R) alteration is located in exon 54 (coding exon 53) of the CDH23 gene. This alteration results from a G to C substitution at nucleotide position 7615, causing the glycine (G) at amino acid position 2539 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001826579 SCV002086848 uncertain significance Usher syndrome type 1 2019-10-28 no assertion criteria provided clinical testing

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