NM_007327.4(GRIN1):c.1975C>T (p.Arg659Trp) AND Intellectual disability, autosomal dominant 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 27, 2022
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:: RCV002526005.4

Allele description [Variation Report for NM_007327.4(GRIN1):c.1975C>T (p.Arg659Trp)]

NM_007327.4(GRIN1):c.1975C>T (p.Arg659Trp)

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.1975C>T (p.Arg659Trp)

HGVS:

NC_000009.12:g.137162701C>T
NG_011507.1:g.28545C>T
NM_000832.7:c.1975C>T
NM_001185090.2:c.2038C>T
NM_001185091.2:c.2038C>T
NM_007327.4:c.1975C>TMANE SELECT
NM_021569.4:c.1975C>T
NP_000823.4:p.Arg659Trp
NP_001172019.1:p.Arg680Trp
NP_001172020.1:p.Arg680Trp
NP_015566.1:p.Arg659Trp
NP_067544.1:p.Arg659Trp
NC_000009.11:g.140057153C>T
NM_007327.3:c.1975C>T

Protein change:

R659W

Links:

dbSNP: rs1064797355

NCBI 1000 Genomes Browser:

rs1064797355

Molecular consequence:

NM_000832.7:c.1975C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001185090.2:c.2038C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001185091.2:c.2038C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007327.4:c.1975C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021569.4:c.1975C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003460786	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 27, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29365063, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003460786

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 27, 2022)

germline

clinical testing

PubMed (2)
[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

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.

Fry AE, Fawcett KA, Zelnik N, Yuan H, Thompson BAN, Shemer-Meiri L, Cushion TD, Mugalaasi H, Sims D, Stoodley N, Chung SK, Rees MI, Patel CV, Brueton LA, Layet V, Giuliano F, Kerr MP, Banne E, Meiner V, Lerman-Sagie T, Helbig KL, Kofman LH, et al.

Brain. 2018 Mar 1;141(3):698-712. doi: 10.1093/brain/awx358.

PubMed [citation]

PMID:: 29365063
PMCID:: PMC5837214

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003460786.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GRIN1 function (PMID: 29365063). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 425473). This missense change has been observed in individual(s) with autosomal dominant GRIN1-related conditions (PMID: 29365063). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 659 of the GRIN1 protein (p.Arg659Trp).

#	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 20, 2024

ClinVar

Relating variation to medicine