Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001322931 | SCV001513826 | uncertain significance | Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53 | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1380 of the SYNJ1 protein (p.Ser1380Phe). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 1022955). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002546098 | SCV003724853 | uncertain significance | Inborn genetic diseases | 2021-11-09 | criteria provided, single submitter | clinical testing | The c.4139C>T (p.S1380F) alteration is located in exon 32 (coding exon 32) of the SYNJ1 gene. This alteration results from a C to T substitution at nucleotide position 4139, causing the serine (S) at amino acid position 1380 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003405545 | SCV004115605 | uncertain significance | SYNJ1-related disorder | 2023-04-11 | criteria provided, single submitter | clinical testing | The SYNJ1 c.4139C>T variant is predicted to result in the amino acid substitution p.Ser1380Phe. This variant has been reported in two individuals with schizophrenia (referred to as p.Ser1341Phe in Rodríguez-López et al. 2017. PubMed ID: 28421333). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-34004005-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |