Submissions for variant NM_006772.3(SYNGAP1):c.490C>T (p.Arg164Ter)

dbSNP: rs1057518352

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412753	SCV000491912	pathogenic	not provided	2023-12-06	criteria provided, single submitter	clinical testing	Identified in two siblings with developmental delay and seizures previously tested at GeneDx who inherited the variant from an unaffected parent who is mosaic; 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34800434, 30541864, 26989088, 28191889, 31031587, 28708303, 37583270)
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris	RCV000496106	SCV000586776	pathogenic	Intellectual disability, autosomal dominant 5	2017-01-06	criteria provided, single submitter	clinical testing	Intellectual disability, severe; epilepsy; autism
CeGaT Center for Human Genetics Tuebingen	RCV000412753	SCV001248668	pathogenic	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496106	SCV001380303	pathogenic	Intellectual disability, autosomal dominant 5	2024-08-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg164*) 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 SYNGAP1-related conditions (PMID: 26989088, 28708303, 30541864). ClinVar contains an entry for this variant (Variation ID: 373327). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000496106	SCV001523724	pathogenic	Intellectual disability, autosomal dominant 5	2020-06-03	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV000496106	SCV002018919	pathogenic	Intellectual disability, autosomal dominant 5	2021-10-08	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000496106	SCV002587098	likely pathogenic	Intellectual disability, autosomal dominant 5	2023-04-18	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PVS1, PS2, PS4_MOD, PM2_SUP
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV000496106	SCV005418861	pathogenic	Intellectual disability, autosomal dominant 5		criteria provided, single submitter	clinical testing	PVS1+PM2_Supporting+PS4_Moderate+PM6
GenomeConnect - Simons Searchlight	RCV001265346	SCV001443465	pathogenic	Complex neurodevelopmental disorder	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 and, in one family, was identified in multiple siblings. Additional phenotypic information for other sibling(s) might be available from Simons Searchlight.