Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000615396 | SCV000712808 | uncertain significance | not specified | 2016-12-13 | criteria provided, single submitter | clinical testing | The p.Cys3306Tyr variant in USH2A has not been reported in individuals with hear ing loss or Usher syndrome. It has been identified in 1/11524 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs758614136); however, its frequency is not high enough to rule out a pathogen ic role. Computational prediction tools and conservation analyses suggest that t his variant may impact the protein, though this information is not predictive en ough to determine pathogenicity. In summary, the clinical significance of the p. Cys3306Tyr variant is uncertain. |
Invitae | RCV001317800 | SCV001508475 | pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 3306 of the USH2A protein (p.Cys3306Tyr). This variant is present in population databases (rs758614136, gnomAD 0.01%). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 505526). 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 expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001317800 | SCV003805944 | uncertain significance | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | 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 |
Natera, |
RCV001829711 | SCV002088379 | uncertain significance | Usher syndrome type 2A | 2020-03-20 | no assertion criteria provided | clinical testing |