NM_007327.4(GRIN1):c.1923G>A (p.Met641Ile) AND Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Clinical significance:Pathogenic (Last evaluated: Feb 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000473483.3

Allele description [Variation Report for NM_007327.4(GRIN1):c.1923G>A (p.Met641Ile)]

NM_007327.4(GRIN1):c.1923G>A (p.Met641Ile)

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.1923G>A (p.Met641Ile)
HGVS:
  • NC_000009.12:g.137162649G>A
  • NG_011507.1:g.28493G>A
  • NM_000832.7:c.1923G>A
  • NM_001185090.2:c.1986G>A
  • NM_001185091.2:c.1986G>A
  • NM_007327.4:c.1923G>AMANE SELECT
  • NM_021569.4:c.1923G>A
  • NP_000823.4:p.Met641Ile
  • NP_001172019.1:p.Met662Ile
  • NP_001172020.1:p.Met662Ile
  • NP_015566.1:p.Met641Ile
  • NP_067544.1:p.Met641Ile
  • NC_000009.11:g.140057101G>A
  • NM_007327.3:c.1923G>A
Protein change:
M641I
Links:
dbSNP: rs1060500046
NCBI 1000 Genomes Browser:
rs1060500046
Molecular consequence:
  • NM_000832.7:c.1923G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185090.2:c.1986G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185091.2:c.1986G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007327.4:c.1923G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021569.4:c.1923G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD)
Synonyms:
Mental retardation, autosomal dominant 8; NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS, WITH OR WITHOUT SEIZURES, AUTOSOMAL DOMINANT
Identifiers:
MONDO: MONDO:0013655; MedGen: C3280282; OMIM: 614254

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000541368Invitaecriteria provided, single submitter
Pathogenic
(Feb 11, 2020)
germlineclinical testing

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

Summary from all submissions

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

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

Electroclinical history of a five-year-old girl with GRIN1-related early-onset epileptic encephalopathy: a video-case study.

Pironti E, Granata F, Cucinotta F, Gagliano A, Efthymiou S, Houlden H, Salpietro V, Di Rosa G.

Epileptic Disord. 2018 Oct 1;20(5):423-427. doi: 10.1684/epd.2018.0992.

PubMed [citation]
PMID:
30355546
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000541368.4

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

Description

This sequence change replaces methionine with isoleucine at codon 641 of the GRIN1 protein (p.Met641Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with early onset epileptic encephalopathy (PMID: 27164704, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Met641 amino acid residue in GRIN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30355546, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

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