Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001199790 | SCV001162730 | pathogenic | Retinitis pigmentosa | 2020-01-09 | criteria provided, single submitter | research | |
Invitae | RCV003558634 | SCV004302084 | pathogenic | not provided | 2023-07-09 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Cys694 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20591486, 28041643; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 813246). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 694 of the USH2A protein (p.Cys694Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with retinitis pigmentosa and/or Usher syndrome (PMID: 25649381, 32531858). |