ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5734C>T (p.Arg1912Trp) (rs397517344)

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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 RCV000039226 SCV000062910 uncertain significance not specified 2012-03-13 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg1912Trp vari ant in CDH23 was identified as a homozygous variant in a patient who was also ho mozygous for the Gly2017Ser variant (Oshima 2008). This suggests that the two v ariants are in cis as observed in this family. Computational analyses (biochemic al amino acid properties, homology, PolyPhen2, SIFT, AlignGVGD) do not provide s trong support for or against pathogenicity and given the predicted splice impact of the Gly2017Ser variant, the Arg1912Trp variant may not contribute to pathoge nicity of the allele. In summary, the clinical significance of this variant in i solation cannot be determined with certainty; however, the allele containing thi s variant and Gly2017Ser, is still likely pathogenic.
Invitae RCV001241540 SCV001414563 uncertain significance not provided 2019-09-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1912 of the CDH23 protein (p.Arg1912Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs397517344, ExAC 0.02%). This variant has been observed in homozygosis in an individual affected with Usher syndrome in whom a second rare homozygous variant in the CDH23 gene was also reported (PMID: 18429043). ClinVar contains an entry for this variant (Variation ID: 45991). 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 C25"). 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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