ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4309C>T (p.Arg1437Ter) (rs397517329)

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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 RCV000039177 SCV000062861 pathogenic Rare genetic deafness 2015-11-16 criteria provided, single submitter clinical testing The p.Arg1437X variant in CDH23 has been previously reported in three unrelated individuals with clinical features of Usher syndrome type 1 who were all compoun d heterozygous with a second CDH23 variant and segregated with disease in an aff ected family member (Roux 2006 and LMM unpublished data). This nonsense variant leads to a premature termination codon at position 1437, which is predicted to l ead to a truncated or absent protein. In summary, this variant meets our criteri a to be classified as pathogenic for Usher syndrome in an autosomal recessive ma nner based on the previous reports and the predicted impact to the protein.
GeneDx RCV000438508 SCV000520441 pathogenic not provided 2016-12-28 criteria provided, single submitter clinical testing The R1437X pathogenic variant in the CDH23 gene has been reported previously in one individual with Usher syndrome type 1 who also harbored a second CDH23 variant in trans (Roux et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1437X variant was not observed in approximately 6300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1437X as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000763214 SCV000893840 pathogenic Deafness, autosomal recessive 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000438508 SCV001419801 pathogenic not provided 2019-11-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1437*) in the CDH23 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs397517329, ExAC 0.01%). This variant has been observed in individual(s) with CDH23-related conditions (PMID: 16679490, 27743452). ClinVar contains an entry for this variant (Variation ID: 45943). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in CDH23 are known to be pathogenic (PMID: 11138009, 21940737). For these reasons, this variant has been classified as Pathogenic.

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