Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001938799 | SCV002203740 | uncertain significance | Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53 | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1436 of the SYNJ1 protein (p.Ile1436Ser). This variant is present in population databases (rs61750218, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SYNJ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1429172). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ce |
RCV002074441 | SCV002496699 | uncertain significance | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | SYNJ1: PM2, BP4 |
Ambry Genetics | RCV004041888 | SCV004961686 | uncertain significance | Inborn genetic diseases | 2021-03-17 | criteria provided, single submitter | clinical testing | The c.4307T>G (p.I1436S) alteration is located in exon 32 (coding exon 32) of the SYNJ1 gene. This alteration results from a T to G substitution at nucleotide position 4307, causing the isoleucine (I) at amino acid position 1436 to be replaced by a serine (S). The p.I1436S alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |