ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.380A>G (p.Asp127Gly) (rs876657754)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel, RCV000710339 SCV000840533 likely pathogenic Usher syndrome 2018-09-10 reviewed by expert panel curation The p.Asp127Gly variant in CDH23 was absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org) (PM2). Computational prediction analysis using the metapredictor tool REVEL suggests that the variant may impact the protein (PP3). This variant has been detected in 1 patient with hearing loss in trans with a pathogenic variant (PM3; Partners LMM internal data SCV000271558.2). The patient with this variant displayed features of congenital severe-profound hearing loss with vestibular dysfunction and ophthalmic findings which are consistent with Usher syndrome (PP4). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recession Usher syndrome based on the ACMG/AMP criteria applied (PM2, PM3, PP3, PP4).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213965 SCV000271558 likely pathogenic Rare genetic deafness 2016-05-23 criteria provided, single submitter clinical testing The p.Asp127Gly variant in CDH23 has been identified by our laboratory highly li kely in trans with a pathogenic variant in CDH23 in an individual with clinical features of Usher syndrome (this individual's family). It has not been identifie d in large population studies. Computational prediction tools and conservation a nalysis suggest that this variant may impact the protein, though this informatio n is not predictive enough to determine pathogenicity. The presence of this vari ant in trans with a pathogenic variant in an individual with Usher syndrome incr eases the likelihood that the p.Asp127Gly variant is pathogenic. In summary, alt hough additional studies are required to fully establish its clinical significan ce, this variant is likely pathogenic.

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