Submissions for variant NM_203446.3(SYNJ1):c.3394G>T (p.Ala1132Ser)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002909399	SCV003257217	uncertain significance	Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53	2022-06-02	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SYNJ1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1171 of the SYNJ1 protein (p.Ala1171Ser).
Neuberg Centre For Genomic Medicine, NCGM	RCV003340556	SCV004048041	uncertain significance	Early-onset Parkinson disease 20		criteria provided, single submitter	clinical testing	The missense c.3394G>T (p.Ala1132Ser) variant in SYNJI gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The amino acid Ala at position 1132 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala1132Ser in SYNJ1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of second reportable variant , the molecular diagnosis is not confirmed.
Ambry Genetics	RCV004066235	SCV004961680	uncertain significance	Inborn genetic diseases	2023-12-16	criteria provided, single submitter	clinical testing	The c.3511G>T (p.A1171S) alteration is located in exon 26 (coding exon 26) of the SYNJ1 gene. This alteration results from a G to T substitution at nucleotide position 3511, causing the alanine (A) at amino acid position 1171 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.