ClinVar Miner

Submissions for variant NM_006772.3(SYNGAP1):c.3415C>T (p.Gln1139Ter)

dbSNP: rs1554122455
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269932 SCV001450298 likely pathogenic not provided 2016-04-07 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003225964 SCV003922238 pathogenic Intellectual disability, autosomal dominant 5 2023-05-02 criteria provided, single submitter curation The heterozygous p.Gln1139Ter variant in SYNGAP1 was identified by our study in one individual with intellectual disability, autism spectrum disorder, seizures, and hypotonia. Trio exome sequencing showed this variant to be de novo. The p.Gln1139Ter variant in SYNGAP1 has been previously reported in 2 unrelated individuals with autosomal dominant SYNGAP1-related disease (ClinVar SCV001443467.1, PMID: 35118825). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. This variant was found to be de novo in two individuals with confirmed paternity and maternity (ClinVar SCV001443467.1, PMID: 35118825). This variant has also been reported in ClinVar (Variation ID: 984836) and has been interpreted as pathogenic by GenomeConnect - Simons Searchlight and as likely pathogenic by Clinical Genetics Karolinska University Hospital,Karolinska University Hospital. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1139, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the SYNGAP1 gene is an established disease mechanism in autosomal dominant intellectual disability 5. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant intellectual disability 5. ACMG/AMP Criteria applied: PVS1, PS4_Supporting, PS2_Moderate, PM2_Supporting (Richards 2015).
GenomeConnect - Simons Searchlight RCV001265348 SCV001443467 pathogenic Complex neurodevelopmental disorder 2018-04-16 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-04-16 and interpreted as Pathogenic. Variant was initially reported on 2018-01-10 by GTR ID of laboratory name 500104. The reporting laboratory might also submit to ClinVar.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.