Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001307078 | SCV001496471 | uncertain significance | Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53 | 2020-10-24 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SYNJ1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 355 of the SYNJ1 protein (p.Gln355His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. |