ClinVar Miner

Submissions for variant NM_006772.3(SYNGAP1):c.1685C>T (p.Pro562Leu)

dbSNP: rs397514670
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254832 SCV000322240 pathogenic not provided 2023-01-23 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: loss of protein function (Berryer et al., 2013; Zeng et al., 2017); Not observed 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: 30541864, 23161826, 28576131, 26989088, 28524815, 33308442, 33639450)
Ambry Genetics RCV000623832 SCV000742372 likely pathogenic Inborn genetic diseases 2017-09-21 criteria provided, single submitter clinical testing
Invitae RCV000034348 SCV000767485 pathogenic Intellectual disability, autosomal dominant 5 2022-08-09 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 41462). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SYNGAP1 function (PMID: 23161826). 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. This missense change has been observed in individual(s) with intellectual disability and epilepsy (PMID: 23161826, 26989088; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 562 of the SYNGAP1 protein (p.Pro562Leu).
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000034348 SCV000782329 uncertain significance Intellectual disability, autosomal dominant 5 2016-11-01 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV002273941 SCV002558898 pathogenic SYNGAP1-related developmental and epileptic encephalopathy criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000254832 SCV004042257 pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing SYNGAP1: PS2, PM2, PS4:Moderate, PP2, PP3
OMIM RCV000034348 SCV000058329 pathogenic Intellectual disability, autosomal dominant 5 2013-02-01 no assertion criteria provided literature only
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV000034348 SCV001427875 likely pathogenic Intellectual disability, autosomal dominant 5 2019-01-01 no assertion criteria provided clinical testing
GenomeConnect - Simons Searchlight RCV001265525 SCV001443669 pathogenic Complex neurodevelopmental disorder 2018-06-01 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-06-01 and interpreted as Pathogenic. Variant was initially reported on 2017-02-13 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
Rare Disease Center, Seoul National University Hospital RCV003156067 SCV003845347 likely pathogenic Autosomal dominant epilepsy 2023-03-23 no assertion criteria provided research

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