Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000513464 | SCV000608548 | uncertain significance | not provided | 2017-06-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000513464 | SCV001417315 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1788 of the CDH23 protein (p.Pro1788Leu). This variant is present in population databases (rs564555435, gnomAD 0.02%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 18429043). ClinVar contains an entry for this variant (Variation ID: 444220). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDH23 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002490863 | SCV002790620 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types | 2021-07-26 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000513464 | SCV001552782 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The CDH23 p.Pro1788Leu variant was identified in the compound heterozygous state in 1 of 112 proband chromosomes (frequency: 0.00893) from individuals or families with Usher I syndrome and was not identified in 192 control chromosomes from healthy individuals (Oshima_2008_PMID:18429043). The variant was identified in dbSNP (ID: rs564555435), ClinVar (classified as a VUS by CeGaT Praxis fuer Humangenetik Tuebingen) and LOVD 3.0 (classified as a VUS by 2 submitters). The variant was identified in control databases in 29 of 275356 chromosomes at a frequency of 0.000105 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 25 of 125208 chromosomes (freq: 0.0002), European (Finnish) in 2 of 24622 chromosomes (freq: 0.000081), African in 1 of 23730 chromosomes (freq: 0.000042) and South Asian in 1 of 30210 chromosomes (freq: 0.000033), but was not observed in the Latino, Ashkenazi Jewish, East Asian or Other populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Pro1788 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. | |
| Natera, |
RCV001829456 | SCV002089430 | uncertain significance | Usher syndrome type 1 | 2020-01-30 | no assertion criteria provided | clinical testing |