ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4391C>T (p.Ala1464Val) (rs374362883)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764918 SCV000896081 uncertain significance Deafness, autosomal recessive 12; Usher syndrome, type 1D; PITUITARY ADENOMA 5, MULTIPLE TYPES 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039181 SCV000062865 uncertain significance not specified 2017-06-28 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala1464Val va riant in CDH23 has been reported in 2 individuals with hearing loss; however in 1 of these individuals had an alternate etiology of the hearing loss identified (Shearer 2013, LMM unpublished data). This variant has also been identified in 0.03% (41/125814) of European chromosomes by the Genome Aggregation Database (gn omAD, http://gnomad.broadinstitute.org/; dbSNP rs374362883); however, its freque ncy is not high enough to rule out a pathogenic role. The alanine (Ala) at posi tion 1464 is not conserved in mammals or evolutionary distant species, with 1 ma mmal (gibbon) having a valine (Val), supporting that a change at this position c ould be tolerated. Additional computational prediction tools and conservation an alyses do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Ala1464Val variant is uncerta in, the conservation data suggests that it is more likely to be benign.

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