Submissions for variant NM_022124.6(CDH23):c.3706C>T (p.Arg1236Ter)

dbSNP: rs397517327

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039163	SCV000062847	pathogenic	Rare genetic deafness	2012-05-29	criteria provided, single submitter	clinical testing	The Arg1236X variant in CDH23 has not been reported in the literature nor previo usly identified by our laboratory. This nonsense variant leads to a premature te rmination codon at position 1236, which is predicted to lead to a truncated or a bsent protein. In summary, this variant meets our criteria to be classified as p athogenic (http://pcpgm.partners.org/LMM).
GeneDx	RCV000482326	SCV000567002	pathogenic	not provided	2015-06-30	criteria provided, single submitter	clinical testing	The R1236X nonsense variant in the CDH23 gene is predicted to cause loss of normal protein functioneither through protein truncation or nonsense-mediated mRNA decay. The R1236X variant was notobserved in approximately 6,200 individuals of European and African American ancestry in the NHLBIExome Sequencing Project, indicating it is not a common benign variant in these populations. Although thisvariant has not been reported previously to our knowledge, we consider it to be pathogenic.
Baylor Genetics	RCV003473276	SCV004212286	pathogenic	Pituitary adenoma 5, multiple types	2023-05-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000482326	SCV004637744	pathogenic	not provided	2023-10-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1236*) 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 (rs397517327, gnomAD 0.003%). 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: 45929). For these reasons, this variant has been classified as Pathogenic.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000482326	SCV001957318	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000482326	SCV001967237	pathogenic	not provided		no assertion criteria provided	clinical testing