Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041694 | SCV000065390 | uncertain significance | not specified | 2008-06-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001852855 | SCV002257447 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 380 of the USH2A protein (p.Tyr380Cys). This variant is present in population databases (rs111033395, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions (PMID: 35266249, 37287646; 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: 48373). 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. |
Ophthalmo- |
RCV002307376 | SCV002600269 | pathogenic | Usher syndrome type 2 | 2022-11-14 | no assertion criteria provided | clinical testing | Novel pathogenic variant. PP4 (manual), PM3 (manual), PM2 , PP3, PP5. https://franklin.genoox.com/clinical-db/variant/snp/chr1-216498651-T-C |