Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000725749 | SCV000339142 | uncertain significance | not provided | 2016-02-01 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000391826 | SCV000731743 | uncertain significance | not specified | 2017-07-11 | criteria provided, single submitter | clinical testing | The p.Pro2742Leu variant in CDH23 has not been previously reported in individual s with hearing loss. It has been reported in an individual with unspecified affe cted status in ClinVar (Variation ID 285919) as of uncertain significance. It ha s also been identified in 9/126192 European chromosomes by the Genome Aggregatio n Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs758360283). Althou gh this variant has been seen in the general population, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro2742Leu variant is un certain. |
Invitae | RCV000725749 | SCV001222435 | uncertain significance | not provided | 2022-08-05 | 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 2742 of the CDH23 protein (p.Pro2742Leu). This variant is present in population databases (rs758360283, gnomAD 0.007%). 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: 285919). 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. |
Gene |
RCV000725749 | SCV001773109 | uncertain significance | not provided | 2023-02-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003243044 | SCV003942644 | uncertain significance | Inborn genetic diseases | 2023-04-26 | criteria provided, single submitter | clinical testing | The c.8225C>T (p.P2742L) alteration is located in exon 58 (coding exon 57) of the CDH23 gene. This alteration results from a C to T substitution at nucleotide position 8225, causing the proline (P) at amino acid position 2742 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001276045 | SCV001461873 | uncertain significance | Usher syndrome type 1 | 2020-01-24 | no assertion criteria provided | clinical testing |