ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.5505G>A (p.Met1835Ile) (rs200786014)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039218 SCV000062902 likely benign not specified 2014-11-10 criteria provided, single submitter clinical testing p.Met1835Ile in exon 43 of CDH23: This variant is not expected to have clinical significance due to a lack of conservation across species. Of note, the platypus and seven bird species have an isoleucine (Ile) at this position despite high n earby amino acid conservation. It has been identified in 0.1% (5/4282) of Africa n American chromosomes by the NHLBI Exome Sequencing Project (; dbSNP rs200786014).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000730090 SCV000857802 uncertain significance not provided 2017-11-08 criteria provided, single submitter clinical testing
Invitae RCV000730090 SCV001392021 uncertain significance not provided 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 1835 of the CDH23 protein (p.Met1835Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs200786014, ExAC 0.2%). This variant has not been reported in the literature in individuals with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 45983). 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.
National Institute on Deafness and Communication Disorders,National Institutes of Health RCV001328021 SCV001519354 uncertain significance Childhood onset hearing loss 2021-07-08 criteria provided, single submitter research BP4 / Modifications from PMID: 30311386 for classification: The genetic causes of hearing loss have not yet been well characterized in the Yoruba population, and the information regarding variant MAF in this population is still limited, so we did not exclude any variant based on their "high" MAF. PP3 criteria was applied even if the REVEL score was below 0.7, if at least two of the pathogenicity prediction algorithms used predicted that the variant was damaging or likely damaging.

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