Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039300 | SCV000062984 | uncertain significance | not specified | 2011-04-27 | criteria provided, single submitter | clinical testing | The Arg3001Gln in CDH23 has not been reported in the literature nor previously i dentified by our laboratory in any other families. Computational analyses (bioch emical amino acid properties, homology, PolyPhen2, SIFT, AlignGVGD) do not provi de strong support for or against pathogenicity. This variant has now been identi fied in this individual and her sibling, both of whom have sensorineural hearing loss. Although this finding is consistent with a causative role, because two si blings have a 50% chance of sharing any variant by chance, the clinical signific ance of this variant still cannot be determined at this time. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000039300 | SCV002511868 | uncertain significance | not specified | 2022-04-29 | criteria provided, single submitter | clinical testing | Variant summary: CDH23 c.9002G>A (p.Arg3001Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 249256 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.9002G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV002490537 | SCV002778925 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 12; Usher syndrome type 1D; Pituitary adenoma 5, multiple types | 2021-11-29 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002513537 | SCV003450339 | uncertain significance | not provided | 2022-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3001 of the CDH23 protein (p.Arg3001Gln). This variant is present in population databases (rs111033467, gnomAD 0.01%). 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: 46064). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. |
| Natera, |
RCV001831681 | SCV002092044 | uncertain significance | Usher syndrome type 1 | 2019-10-28 | no assertion criteria provided | clinical testing |