SYNGAP1 was first reported in relation to AD nonsyndromic intellectual disability in 2009 (Hamdan et al, 2009). At least 129 unique variants (e.g. missense, in-frame indel, nonsense, frameshift, large deletion, complex rearrangement, etc) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. While a large number of pathogenic (mostly de novo) variants have been identified in patients with a complex neurodevelopmental disorder, there appears to be little correlation between variant location and severity of ID, epilepsy, or autism symptoms. In summary, SYNGAP1 is definitively associated with AD complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the Epilepsy GCEP on 4/2/2019.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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