Submissions for variant NM_203446.3(SYNJ1):c.3097T>C (p.Ser1033Pro)

gnomAD frequency: 0.00011  dbSNP: rs61752559

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000704245	SCV000833186	uncertain significance	Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1072 of the SYNJ1 protein (p.Ser1072Pro). This variant is present in population databases (rs61752559, gnomAD 0.01%). 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: 580644). 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 with a negative predictive value of 80%. 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.
Baylor Genetics	RCV001333169	SCV001525681	uncertain significance	Developmental and epileptic encephalopathy, 53	2018-01-25	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV003223673	SCV003919610	uncertain significance	not provided	2022-10-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003303185	SCV004003524	uncertain significance	Inborn genetic diseases	2023-04-25	criteria provided, single submitter	clinical testing	The c.3214T>C (p.S1072P) alteration is located in exon 24 (coding exon 24) of the SYNJ1 gene. This alteration results from a T to C substitution at nucleotide position 3214, causing the serine (S) at amino acid position 1072 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.