ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.8G>A (p.Arg3His) (rs397517363)

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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 RCV000039299 SCV000062983 uncertain significance not specified 2019-06-26 criteria provided, single submitter clinical testing The p.Arg3His variant in CDH23 has been previously reported by our laboratory with one individual with hearing loss and delayed walking. This individual also harbored a second variant of uncertain significance in CDH23, but testing of parents to determine phasing was not performed. The p.Arg3His variant has been identified 0.02% (6/23796) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Invitae RCV001248760 SCV001422269 uncertain significance not provided 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 3 of the CDH23 protein (p.Arg3His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs397517363, ExAC 0.02%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 46063). 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: "Tolerated"; 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.

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