Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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 (http://evs.gs.wash ington.edu/EVS/; dbSNP rs200786014). |
Eurofins Ntd Llc |
RCV000730090 | SCV000857802 | uncertain significance | not provided | 2017-11-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000730090 | SCV001392021 | uncertain significance | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1835 of the CDH23 protein (p.Met1835Ile). This variant is present in population databases (rs200786014, gnomAD 0.2%). 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: 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, |
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. |