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NM_007327.4(GRIN1):c.1984G>A (p.Glu662Lys) AND Intellectual disability, autosomal dominant 8

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 11, 2011
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000022577.28

Allele description [Variation Report for NM_007327.4(GRIN1):c.1984G>A (p.Glu662Lys)]

NM_007327.4(GRIN1):c.1984G>A (p.Glu662Lys)

Gene:
GRIN1:glutamate ionotropic receptor NMDA type subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.3
Genomic location:
Preferred name:
NM_007327.4(GRIN1):c.1984G>A (p.Glu662Lys)
HGVS:
  • NC_000009.12:g.137162710G>A
  • NG_011507.1:g.28554G>A
  • NM_000832.7:c.1984G>A
  • NM_001185090.2:c.2047G>A
  • NM_001185091.2:c.2047G>A
  • NM_007327.4:c.1984G>AMANE SELECT
  • NM_021569.4:c.1984G>A
  • NP_000823.4:p.Glu662Lys
  • NP_001172019.1:p.Glu683Lys
  • NP_001172020.1:p.Glu683Lys
  • NP_015566.1:p.Glu662Lys
  • NP_067544.1:p.Glu662Lys
  • NC_000009.11:g.140057162G>A
  • NM_007327.3:c.1984G>A
  • Q05586:p.Glu662Lys
Protein change:
E662K; GLU662LYS
Links:
UniProtKB: Q05586#VAR_066598; OMIM: 138249.0001; dbSNP: rs387906635
NCBI 1000 Genomes Browser:
rs387906635
Molecular consequence:
  • NM_000832.7:c.1984G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185090.2:c.2047G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185091.2:c.2047G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007327.4:c.1984G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021569.4:c.1984G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Intellectual disability, autosomal dominant 8 (NDHMSD)
Synonyms:
Mental retardation, autosomal dominant 8; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
Identifiers:
MONDO: MONDO:0013655; MedGen: C3280282; OMIM: 614254

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000043866OMIM
no assertion criteria provided
Pathogenic
(Mar 11, 2011) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy.

Lemke JR, Geider K, Helbig KL, Heyne HO, Schütz H, Hentschel J, Courage C, Depienne C, Nava C, Heron D, Møller RS, Hjalgrim H, Lal D, Neubauer BA, Nürnberg P, Thiele H, Kurlemann G, Arnold GL, Bhambhani V, Bartholdi D, Pedurupillay CR, Misceo D, et al.

Neurology. 2016 Jun 7;86(23):2171-8. doi: 10.1212/WNL.0000000000002740. Epub 2016 May 6.

PubMed [citation]
PMID:
27164704
PMCID:
PMC4898312

Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O; S2D Group., Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, et al.

Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub 2011 Mar 3. Erratum in: Am J Hum Genet. 2011 Apr 8;88(4):516.

PubMed [citation]
PMID:
21376300
PMCID:
PMC3059427

Details of each submission

From OMIM, SCV000043866.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a 10-year-old girl with autosomal dominant neurodevelopmental disorder without hyperkinetic movements or seizures (NDHMSD; 614254), Hamdan et al. (2011) identified a de novo heterozygous c.1984G-A transition (c.1984G-A, NM_007327.3) in the GRIN1 gene, resulting in a glu662-to-lys (E662K) substitution. The patient had a normal neural exam and normal brain imaging by CT scan, and there was no evidence of epilepsy. Functional studies in Xenopus oocytes showed that this mutation produced a significant increase in NMDAR-induced calcium currents; excessive calcium influx through NMDAR could lead to excitotoxic neuronal cell damage. This mutation was not identified in 285 healthy controls.

Lemke et al. (2016) noted that the patient reported by Hamdan et al. (2011) with the E662K mutation had the mildest phenotype when compared to 22 other patients with GRIN1 mutations. E662K is located in the S2 ligand-binding domain; this was the only patient reported with a mutation in this domain.

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

Last Updated: Aug 5, 2023