Submissions for variant NM_203446.3(SYNJ1):c.2250T>A (p.Asn750Lys)

gnomAD frequency: 0.00005  dbSNP: rs570501803

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000809591	SCV000949749	uncertain significance	Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53	2023-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 789 of the SYNJ1 protein (p.Asn789Lys). This variant is present in population databases (rs570501803, gnomAD 0.03%). 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: 653769). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SYNJ1 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	RCV002538056	SCV003739928	uncertain significance	Inborn genetic diseases	2021-11-16	criteria provided, single submitter	clinical testing	The c.2367T>A (p.N789K) alteration is located in exon 18 (coding exon 18) of the SYNJ1 gene. This alteration results from a T to A substitution at nucleotide position 2367, causing the asparagine (N) at amino acid position 789 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004773178	SCV005384820	uncertain significance	not provided	2024-02-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
GenomeConnect - Invitae Patient Insights Network	RCV003483735	SCV004228976	not provided	Developmental and epileptic encephalopathy, 1		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 03-06-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.