Submissions for variant NM_006772.3(SYNGAP1):c.1030G>A (p.Gly344Ser)

dbSNP: rs1760893537

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001260588	SCV001437659	pathogenic	Intellectual disability, autosomal dominant 5		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001260588	SCV003459961	pathogenic	Intellectual disability, autosomal dominant 5	2024-05-10	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 344 of the SYNGAP1 protein (p.Gly344Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epileptic encephalopathy with cerebellar atrophy (PMID: 29778030, 30541864). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 981240). 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 expected to disrupt SYNGAP1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV003985487	SCV005327186	pathogenic	not provided	2023-07-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29778030, 30541864)
GenomeConnect - Simons Searchlight	RCV001265527	SCV001443671	likely pathogenic	Complex neurodevelopmental disorder	2019-03-25	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-03-25 and interpreted as Likely Pathogenic. Variant was initially reported on 2015-12-08 by GTR ID of laboratory name 500105. The reporting laboratory might also submit to ClinVar.
GenomeConnect - Brain Gene Registry	RCV003985487	SCV004801639	not provided	not provided		no assertion provided	phenotyping only	Variant classified as Likely pathogenic and reported on 12-08-2015 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/.