ClinVar Miner

Submissions for variant NM_006950.3(SYN1):c.1961G>A (p.Gly654Glu) (rs749342768)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189662 SCV000243308 uncertain significance not provided 2014-07-08 criteria provided, single submitter clinical testing p.Gly654Glu (GGA>GAA): c.1961 G>A in exon 12 of the SYN1 gene (NM_133499.2) A variant of unknown significance has been identified in the SYN1 gene. The G654E variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 5,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G654E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Fulgent Genetics,Fulgent Genetics RCV000766094 SCV000897569 uncertain significance Epilepsy, X-linked, with variable learning disabilities and behavior disorders 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000766094 SCV001374437 uncertain significance Epilepsy, X-linked, with variable learning disabilities and behavior disorders 2019-08-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 654 of the SYN1 protein (p.Gly654Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SYN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 207477). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.

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