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NM_007327.4(GRIN1):c.2005G>C (p.Asp669His) AND Intellectual disability, autosomal dominant 8

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 11, 2020
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:
RCV001954055.6

Allele description [Variation Report for NM_007327.4(GRIN1):c.2005G>C (p.Asp669His)]

NM_007327.4(GRIN1):c.2005G>C (p.Asp669His)

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.2005G>C (p.Asp669His)
HGVS:
  • NC_000009.12:g.137162731G>C
  • NG_011507.1:g.28575G>C
  • NM_000832.7:c.2005G>C
  • NM_001185090.2:c.2068G>C
  • NM_001185091.2:c.2068G>C
  • NM_007327.4:c.2005G>CMANE SELECT
  • NM_021569.4:c.2005G>C
  • NP_000823.4:p.Asp669His
  • NP_001172019.1:p.Asp690His
  • NP_001172020.1:p.Asp690His
  • NP_015566.1:p.Asp669His
  • NP_067544.1:p.Asp669His
  • NC_000009.11:g.140057183G>C
Protein change:
D669H
Links:
dbSNP: rs2131299466
NCBI 1000 Genomes Browser:
rs2131299466
Molecular consequence:
  • NM_000832.7:c.2005G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185090.2:c.2068G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001185091.2:c.2068G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007327.4:c.2005G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021569.4:c.2005G>C - 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
SCV002244192Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 11, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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, SCV002244192.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant has not been reported in the literature in individuals with GRIN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 669 of the GRIN1 protein (p.Asp669His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine.

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

Last Updated: Sep 29, 2024