Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001977051 | SCV002271068 | uncertain significance | Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 459 of the SYNJ1 protein (p.Arg459His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of early-onset Parkinson disease (PMID: 32707456). ClinVar contains an entry for this variant (Variation ID: 1488630). 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 SYNJ1 protein function. This variant disrupts the p.Arg459 amino acid residue in SYNJ1. Other variant(s) that disrupt this residue have been observed in individuals with SYNJ1-related conditions (PMID: 27496670), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |