NM_007327.4(GRIN1):c.2443G>A (p.Gly815Arg) AND Intellectual disability, autosomal dominant 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 30, 2023
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:: RCV003528151.2

Allele description [Variation Report for NM_007327.4(GRIN1):c.2443G>A (p.Gly815Arg)]

NM_007327.4(GRIN1):c.2443G>A (p.Gly815Arg)

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.2443G>A (p.Gly815Arg)

HGVS:

NC_000009.12:g.137163668G>A
NG_011507.1:g.29512G>A
NM_000832.7:c.2443G>A
NM_001185090.2:c.2506G>A
NM_001185091.2:c.2506G>A
NM_007327.4:c.2443G>AMANE SELECT
NM_021569.4:c.2443G>A
NP_000823.4:p.Gly815Arg
NP_001172019.1:p.Gly836Arg
NP_001172020.1:p.Gly836Arg
NP_015566.1:p.Gly815Arg
NP_067544.1:p.Gly815Arg
NC_000009.11:g.140058120G>A
NM_007327.3:c.2443G>A

Protein change:

G815R

Links:

dbSNP: rs797044925

NCBI 1000 Genomes Browser:

rs797044925

Molecular consequence:

NM_000832.7:c.2443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001185090.2:c.2506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001185091.2:c.2506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007327.4:c.2443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021569.4:c.2443G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295627	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25864721, 27164704, 32827528, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295627

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 30, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

Ohba C, Shiina M, Tohyama J, Haginoya K, Lerman-Sagie T, Okamoto N, Blumkin L, Lev D, Mukaida S, Nozaki F, Uematsu M, Onuma A, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Kato M, Ogata K, Saitsu H, Matsumoto N.

Epilepsia. 2015 Jun;56(6):841-8. doi: 10.1111/epi.12987. Epub 2015 Apr 10.

PubMed [citation]

PMID:: 25864721

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

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295627.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 815 of the GRIN1 protein (p.Gly815Arg). This variant also falls at the last nucleotide of exon 17, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GRIN1-related conditions (PMID: 25864721, 27164704, 32827528). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 208743). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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