Submissions for variant NM_006772.3(SYNGAP1):c.2059C>T (p.Arg687Ter)

dbSNP: rs1060503383

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000477576	SCV000552812	pathogenic	Intellectual disability, autosomal dominant 5	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg687*) 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 clinical features of SYNGAP1-related conditions (PMID: 30440138, 30541864). ClinVar contains an entry for this variant (Variation ID: 411584). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000498682	SCV000590249	pathogenic	not provided	2024-09-11	criteria provided, single submitter	clinical testing	Published functional studies demonstrate significantly decreased protein stability and altered subcellular localization (PMID: 33308442); Not observed in large population cohorts (gnomAD); Nonsense 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; This variant is associated with the following publications: (PMID: 30541864, 30440138, 33308442, 32913957, 33639450, 31440721, 35390071, 34924933, 33057194, 36583017, 35982159)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000626901	SCV000747604	likely pathogenic	Motor delay; Atypical behavior; Aggressive behavior; Ptosis; Pointed chin; Abnormal sternum morphology; Delayed speech and language development; Downslanted palpebral fissures; Triangular face; Wide nasal bridge; High forehead; Bulbous tips of toes; Infantile muscular hypotonia	2017-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000477576	SCV000893716	pathogenic	Intellectual disability, autosomal dominant 5	2018-10-31	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000477576	SCV001934332	pathogenic	Intellectual disability, autosomal dominant 5	2020-11-19	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV003128403	SCV003804855	pathogenic	See cases	2022-10-10	criteria provided, single submitter	clinical testing	ACMG categories: PVS1,PM2,PP5
Molecular Genetics Lab, CHRU Brest	RCV000477576	SCV004697776	pathogenic	Intellectual disability, autosomal dominant 5		criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000477576	SCV004809463	likely pathogenic	Intellectual disability, autosomal dominant 5	2024-04-04	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000498682	SCV005198380	pathogenic	not provided	2022-08-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000498682	SCV001809152	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000498682	SCV001957549	pathogenic	not provided		no assertion criteria provided	clinical testing