Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041895 | SCV000065591 | uncertain significance | not specified | 2012-04-10 | criteria provided, single submitter | clinical testing | The Pro2241Ser variant in USH2A has not been reported in the literature nor prev iously identified by our laboratory. Computational analyses (biochemical amino a cid properties, conservation, PolyPhen2, SIFT, AlignGVGD) suggest that the varia nt may impact the protein. However, this information is not predictive enough to determine pathogenicity. It should also be noted that this variant was identifi ed in cis with the Cys759Phe USH2A variant. In summary, the clinical significanc e of this variant cannot be determined with certainty at this time. |
| Labcorp Genetics |
RCV001210033 | SCV001381497 | likely pathogenic | not provided | 2024-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2241 of the USH2A protein (p.Pro2241Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa (internal data). ClinVar contains an entry for this variant (Variation ID: 48569). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. This variant disrupts the p.Pro2241 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25999674, 26927203, 27318125, 28224992; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Natera, |
RCV001274250 | SCV001458130 | uncertain significance | Usher syndrome type 2A | 2020-09-16 | no assertion criteria provided | clinical testing |