ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: rs397517329
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham 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d heterozygous with a second CDH23 variant and segregated with disease in an aff ected family member (Roux 2006 and LMM unpublished data).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 2022-03-17 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16679490, 27743452, 31980526, 32037395)
Fulgent Genetics, Fulgent Genetics RCV000763214 SCV000893840 pathogenic Autosomal recessive nonsyndromic hearing loss 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 2023-12-06 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. Loss-of-function variants in CDH23 are known to be pathogenic (PMID: 11138009, 21940737). This variant is present in population databases (rs397517329, gnomAD 0.004%). This premature translational stop signal 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 disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003473277 SCV004210604 pathogenic Pituitary adenoma 5, multiple types 2023-10-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV001831667 SCV002093879 pathogenic Usher syndrome type 1 2021-07-07 no assertion criteria provided clinical testing

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