Submissions for variant NM_022124.6(CDH23):c.7908C>G (p.Tyr2636Ter)

dbSNP: rs878853337

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760510	SCV000890401	pathogenic	not provided	2018-10-19	criteria provided, single submitter	clinical testing	The Y2636X nonsense variant in the CDH23 gene has been observed in the heterozygous state previously in association with Usher syndrome (Ellingford et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant is not observed in large population cohorts (Lek et al., 2016). In summary, we classify this variant as pathogenic.
Invitae	RCV000760510	SCV002138410	pathogenic	not provided	2023-11-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr2636*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CDH23-related conditions (PMID: 27208204). ClinVar contains an entry for this variant (Variation ID: 236430). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003475052	SCV004210591	pathogenic	Pituitary adenoma 5, multiple types	2023-10-21	criteria provided, single submitter	clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225547	SCV000282536	likely pathogenic	Retinal dystrophy		no assertion criteria provided	clinical testing