ClinVar Miner

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

dbSNP: rs1060503383
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477576 SCV000552812 pathogenic Intellectual disability, autosomal dominant 5 2023-08-16 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 2017-06-05 criteria provided, single submitter clinical testing The R687X variant in the SYNGAP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R687X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R687X as a pathogenic variant.
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
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

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