ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.3115G>A (p.Val1039Met)

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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 RCV001195489 SCV001365866 uncertain significance not specified 2019-08-12 criteria provided, single submitter clinical testing The p.Val1039Met variant in CDH23 has been previously reported in 1 individual with Usher syndrome who also had a second variant in CDH23, though it does not appear that phasing was performed (Fuster Garcia 2018). It has also been identified in 0.02% (26/112538) of European 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 the p.Val1039Met variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, BP4.
Invitae RCV001245604 SCV001418902 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1039 of the CDH23 protein (p.Val1039Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs781597943, ExAC 0.02%). This variant has been observed in an individual affected with Usher syndrome (PMID: 30459346). 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.

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