ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.2341G>A (p.Ala781Thr) (rs375918283)

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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 RCV000155046 SCV000204730 uncertain significance not specified 2013-12-05 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ala781Thr varia nt in CDH23 has not been previously reported in individuals with hearing loss, b ut was identified in 0.04% (2/4214) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; rs37591828). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the Ala781Thr variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant cannot be determined with c ertainty; however based upon the arguments described above, we would lean toward s a more likely benign role.
Invitae RCV001051031 SCV001215164 uncertain significance not provided 2019-09-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 781 of the CDH23 protein (p.Ala781Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs375918283, ExAC 0.1%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 178302). 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 C55"). 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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