Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003738028 | SCV004551498 | likely pathogenic | not provided | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 4765 of the USH2A protein (p.Val4765Ala). This variant is present in population databases (rs763127023, gnomAD 0.006%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 30054919; 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: 978999). 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 not expected to disrupt USH2A protein function with a negative predictive value of 95%. 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. |
| Faculty of Health Sciences, |
RCV001257872 | SCV001434719 | pathogenic | Autosomal recessive retinitis pigmentosa | 2018-09-03 | no assertion criteria provided | literature only |