Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001060016 | SCV001224676 | pathogenic | not provided | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr1587Cysfs*4) 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 (rs759981467, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 27743452). ClinVar contains an entry for this variant (Variation ID: 854878). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV001267073 | SCV001445254 | pathogenic | Inborn genetic diseases | 2021-01-15 | criteria provided, single submitter | clinical testing | The c.4759_4766delACACGGCC (p.T1587Cfs*4) alteration, located in exon 38 (coding exon 37) of the CDH23 gene, consists of a deletion of 8 nucleotides from position 4759 to 4766, causing a translational frameshift with a predicted alternate stop codon after 4 amino acids. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the CDH23 c.4759_4766delACACGGCC alteration was observed in 0.0022% (6/274,206) total alleles studied, with a frequency of 0.0048% (6/124,894) in the European (non-Finnish) subpopulation. This alteration has been seen with a missense variant in a 6 year old patient with retinal dystrophy on a fundoscopic exam, rod-cone dystrophy on electroretinogram, and vestibular impairment. The phase of missense variant and this alteration was not provided (Kletke, 2017). Based on the available evidence, this alteration is classified as pathogenic. |
| Gene |
RCV001060016 | SCV002552602 | pathogenic | not provided | 2022-07-22 | criteria provided, single submitter | clinical testing | Observed with a pathogenic variant on the opposite allele (in trans) in a patient with bilateral congenital sensorineural hearing loss referred for genetic testing at GeneDx; Reported with a second variant (phase unknown) in unrelated patients with Usher syndrome or a combination of sensorineural hearing loss and vestibular impairment in published literature (Schultz et al., 2011; Bonnet et al., 2016; Kletke et al., 2017); Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11138009, 21940737, 27743452, 27460420) |
| Baylor Genetics | RCV003473670 | SCV004212319 | pathogenic | Pituitary adenoma 5, multiple types | 2024-02-17 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001832538 | SCV002089241 | pathogenic | Usher syndrome type 1 | 2021-07-26 | no assertion criteria provided | clinical testing |