ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.7685C>T (p.Ser2562Leu)

gnomAD frequency: 0.00001  dbSNP: rs538435711
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726844 SCV000703587 uncertain significance not provided 2016-12-06 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000597063 SCV000731485 uncertain significance not specified 2018-10-30 criteria provided, single submitter clinical testing The p.Ser2562Leu variant in CDH23 has been previously reported by our laboratory in one individual with hearing loss; however, this individual had a likely alte rnate explanation for their hearing loss (compound heterozygous likely pathogeni c variants in LARS2). The p.Ser2562Leu variant has also been identified in 0.02% (6/28768) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.or g) and has been reported in ClinVar (Variation ID 498532). Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser256 2Leu variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
Invitae RCV000726844 SCV003448208 uncertain significance not provided 2022-05-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2562 of the CDH23 protein (p.Ser2562Leu). This variant is present in population databases (rs538435711, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 498532). 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.
Natera, Inc. RCV001276914 SCV001463571 uncertain significance Usher syndrome type 1 2020-09-16 no assertion criteria provided clinical testing

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