Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000655767 | SCV000777698 | uncertain significance | Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53 | 2022-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1176 of the SYNJ1 protein (p.Pro1176Leu). This variant is present in population databases (rs569046864, gnomAD 0.05%). 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: 544570). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002536309 | SCV003688039 | uncertain significance | Inborn genetic diseases | 2022-02-10 | criteria provided, single submitter | clinical testing | The c.3527C>T (p.P1176L) alteration is located in exon 26 (coding exon 26) of the SYNJ1 gene. This alteration results from a C to T substitution at nucleotide position 3527, causing the proline (P) at amino acid position 1176 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003411559 | SCV004115421 | uncertain significance | SYNJ1-related disorder | 2023-04-11 | criteria provided, single submitter | clinical testing | The SYNJ1 c.3527C>T variant is predicted to result in the amino acid substitution p.Pro1176Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.056% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-34017298-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV004588083 | SCV005080237 | uncertain significance | not provided | 2023-11-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a patient with epilepsy in the published literature, however, a second variant was not reported (PMID: 36539902); This variant is associated with the following publications: (PMID: 36539902) |