NM_007327.4(GRIN1):c.1736del (p.Leu579fs) AND Intellectual disability, autosomal dominant 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 11, 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:: RCV003644035.2

Allele description [Variation Report for NM_007327.4(GRIN1):c.1736del (p.Leu579fs)]

NM_007327.4(GRIN1):c.1736del (p.Leu579fs)

Gene:

GRIN1:glutamate ionotropic receptor NMDA type subunit 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_007327.4(GRIN1):c.1736del (p.Leu579fs)

HGVS:

NC_000009.12:g.137162275del
NG_011507.1:g.28119del
NM_000832.7:c.1736del
NM_001185090.2:c.1799del
NM_001185091.2:c.1799del
NM_007327.4:c.1736delMANE SELECT
NM_021569.4:c.1736del
NP_000823.4:p.Leu579fs
NP_001172019.1:p.Leu600fs
NP_001172020.1:p.Leu600fs
NP_015566.1:p.Leu579fs
NP_067544.1:p.Leu579fs
NC_000009.11:g.140056727del

Protein change:

L579fs

Molecular consequence:

NM_000832.7:c.1736del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001185090.2:c.1799del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001185091.2:c.1799del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007327.4:c.1736del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021569.4:c.1736del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004432307	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27164704, 35393335, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004432307

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 11, 2023)

germline

clinical testing

PubMed (3)
[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

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

Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B.

Brock S, Laquerriere A, Marguet F, Myers SJ, Hongjie Y, Baralle D, Vanderhasselt T, Stouffs K, Keymolen K, Kim S, Allen J, Shaulsky G, Chelly J, Marcorelle P, Aziza J, Villard L, Sacaze E, de Wit MCY, Wilke M, Mancini GMS, Hehr U, Lim D, et al.

J Med Genet. 2023 Feb;60(2):183-192. doi: 10.1136/jmedgenet-2021-107971. Epub 2022 Apr 7.

PubMed [citation]

PMID:: 35393335
PMCID:: PMC10642159

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004432307.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu579Argfs*13) in the GRIN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRIN1 are known to be pathogenic (PMID: 27164704, 35393335). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN1-related conditions. 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: Sep 29, 2024

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