Submissions for variant NM_203446.3(SYNJ1):c.2254G>T (p.Asp752Tyr)

gnomAD frequency: 0.00010  dbSNP: rs145978776

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000695137	SCV000823618	uncertain significance	Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 791 of the SYNJ1 protein (p.Asp791Tyr). This variant is present in population databases (rs145978776, 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: 573462). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SYNJ1 protein function. 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.
GeneDx	RCV001529862	SCV001778957	uncertain significance	not provided	2019-03-06	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003163190	SCV003864991	uncertain significance	Inborn genetic diseases	2023-01-10	criteria provided, single submitter	clinical testing	The c.2371G>T (p.D791Y) alteration is located in exon 18 (coding exon 18) of the SYNJ1 gene. This alteration results from a G to T substitution at nucleotide position 2371, causing the aspartic acid (D) at amino acid position 791 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529862	SCV001744063	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529862	SCV001972727	uncertain significance	not provided		no assertion criteria provided	clinical testing