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NM_006772.3(SYNGAP1):c.1630C>T (p.Arg544Ter) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 26, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002529771.3

Allele description [Variation Report for NM_006772.3(SYNGAP1):c.1630C>T (p.Arg544Ter)]

NM_006772.3(SYNGAP1):c.1630C>T (p.Arg544Ter)

Genes:
SYNGAP1-AS1:SYNGAP1 antisense RNA 1 [Gene - HGNC]
SYNGAP1:synaptic Ras GTPase activating protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.32
Genomic location:
Preferred name:
NM_006772.3(SYNGAP1):c.1630C>T (p.Arg544Ter)
HGVS:
  • NC_000006.12:g.33438873C>T
  • NG_016137.2:g.23804C>T
  • NM_001130066.2:c.1630C>T
  • NM_006772.3:c.1630C>TMANE SELECT
  • NP_001123538.1:p.Arg544Ter
  • NP_006763.2:p.Arg544Ter
  • LRG_1193t1:c.1630C>T
  • LRG_1193:g.23804C>T
  • LRG_1193p1:p.Arg544Ter
  • NC_000006.11:g.33406650C>T
  • NM_006772.2:c.1630C>T
  • p.R544X
Protein change:
R544*
Links:
dbSNP: rs1554121443
NCBI 1000 Genomes Browser:
rs1554121443
Molecular consequence:
  • NM_001130066.2:c.1630C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006772.3:c.1630C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003568417Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 26, 2021) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.

Mignot C, von Stülpnagel C, Nava C, Ville D, Sanlaville D, Lesca G, Rastetter A, Gachet B, Marie Y, Korenke GC, Borggraefe I, Hoffmann-Zacharska D, Szczepanik E, Rudzka-Dybała M, Yiş U, Çağlayan H, Isapof A, Marey I, Panagiotakaki E, Korff C, Rossier E, Riess A, et al.

J Med Genet. 2016 Aug;53(8):511-22. doi: 10.1136/jmedgenet-2015-103451. Epub 2016 Mar 17. Erratum in: J Med Genet. 2016 Oct;53(10):720.

PubMed [citation]
PMID:
26989088

A clinical survey of mosaic single nucleotide variants in disease-causing genes detected by exome sequencing.

Cao Y, Tokita MJ, Chen ES, Ghosh R, Chen T, Feng Y, Gorman E, Gibellini F, Ward PA, Braxton A, Wang X, Meng L, Xiao R, Bi W, Xia F, Eng CM, Yang Y, Gambin T, Shaw C, Liu P, Stankiewicz P.

Genome Med. 2019 Jul 26;11(1):48. doi: 10.1186/s13073-019-0658-2.

PubMed [citation]
PMID:
31349857
PMCID:
PMC6660700
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003568417.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The c.1630C>T (p.R544*) alteration, located in exon 10 (coding exon 10) of the SYNGAP1 gene, consists of a C to T substitution at nucleotide position 1630. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 544. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported to occur de novo in a patient with severe intellectual disability, truncal hypotonia, swallowing difficulties, epilepsy, and very poor social interactions (Mignot, 2016). In addition, this alteration has also been identified in a patient with generalized epilepsy (Hoelz, 2020) and in a mosaic patient with a neurodevelopmental phenotype (Cao, 2019). Based on the available evidence, this alteration is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024