Submissions for variant NM_006772.3(SYNGAP1):c.333del (p.Lys114fs)

dbSNP: rs1131691979

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493489	SCV000583260	pathogenic	not provided	2023-06-20	criteria provided, single submitter	clinical testing	Reported previously in the heterozygous state in a patient with epileptic encephalopathy, moderate intellectual disability, and autism spectrum disorder (Carvill et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31395010, 25418537, 30541864, 23708187, 31440721)
Ambry Genetics	RCV000624491	SCV000742364	pathogenic	Inborn genetic diseases	2017-04-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000689750	SCV000817416	pathogenic	Intellectual disability, autosomal dominant 5	2024-10-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys114Serfs*20) in the SYNGAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23161826, 23708187, 26989088). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autism and/or intellectual disability (PMID: 25418537). ClinVar contains an entry for this variant (Variation ID: 430456). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000493489	SCV001905639	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000493489	SCV002072200	pathogenic	not provided	2017-09-21	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000689750	SCV002549834	pathogenic	Intellectual disability, autosomal dominant 5	2022-06-22	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PVS1, PS4, PM2_SUP, PP3
GenomeConnect - Simons Searchlight	RCV001265345	SCV001443464	pathogenic	Infantile epilepsy syndrome	2018-04-27	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-04-27 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000689750	SCV001519038	pathogenic	Intellectual disability, autosomal dominant 5		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000493489	SCV002035359	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000493489	SCV002037527	pathogenic	not provided		no assertion criteria provided	clinical testing
GenomeConnect - Brain Gene Registry	RCV000689750	SCV004801640	not provided	Intellectual disability, autosomal dominant 5		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 09-23-2014 by Fulgent Diagnostics . Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.