ClinVar Miner

Submissions for variant NM_006772.3(SYNGAP1):c.2225G>A (p.Arg742Gln)

gnomAD frequency: 0.00001  dbSNP: rs959800067
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192381 SCV001360452 uncertain significance not specified 2019-07-24 criteria provided, single submitter clinical testing Variant summary: SYNGAP1 c.2225G>A (p.Arg742Gln) results in a conservative amino acid change located in the DUF3498 (unknown function) domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250810 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2225G>A in individuals affected with mental retardation and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003507369 SCV004277472 uncertain significance Intellectual disability, autosomal dominant 5 2023-04-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 928481). 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 SYNGAP1 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 742 of the SYNGAP1 protein (p.Arg742Gln).

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