Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317244 | SCV004021190 | uncertain significance | not specified | 2023-06-22 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.4136G>T (p.Arg1379Leu) results in a non-conservative amino acid change located in a calcium binding site of extracellular cadherin 13 domain (Zhang_2017) of the encoded protein sequence. This alters a highly conserved residue in which another missense variant (p.R1379P) has been found in association with Usher syndrome (HGMD). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245062 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4136G>T has been reported in the literature in related heterozygous individuals affected with pituitary adenoma without a second variant identified and without retinal phenotyping (Zhang_2017). This reports does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28413019). One submitter (OMIM) has cited a clinical-significance assessment for this variant to ClinVar after 2014 under the condition of pituitary adenoma, and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000504588 | SCV000598643 | pathogenic | Pituitary adenoma 5, multiple types | 2017-09-26 | no assertion criteria provided | literature only |