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NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln) AND Sleep myoclonus

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 7, 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:
RCV001256113.3

Allele description [Variation Report for NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln)]

NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln)

Gene:
GLRA1:glycine receptor alpha 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q33.1
Genomic location:
Preferred name:
NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln)
Other names:
R271Q
HGVS:
  • NC_000005.10:g.151851406C>T
  • NG_011764.1:g.78431G>A
  • NM_000171.4:c.896G>AMANE SELECT
  • NM_001146040.2:c.896G>A
  • NM_001292000.2:c.647G>A
  • NP_000162.2:p.Arg299Gln
  • NP_001139512.1:p.Arg299Gln
  • NP_001278929.1:p.Arg216Gln
  • NC_000005.9:g.151230967C>T
  • NM_000171.3:c.896G>A
  • NM_001146040.1:c.896G>A
  • P23415:p.Arg299Gln
Nucleotide change:
G1192A
Protein change:
R216Q; ARG271GLN
Links:
UniProtKB: P23415#VAR_000299; OMIM: 138491.0002; dbSNP: rs121918408
NCBI 1000 Genomes Browser:
rs121918408
Molecular consequence:
  • NM_000171.4:c.896G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001146040.2:c.896G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001292000.2:c.647G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Sleep myoclonus
Identifiers:
MedGen: C0751352; Human Phenotype Ontology: HP:0012323

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001432901New York Genome Center - CSER-NYCKidSeq
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Pathogenic
(Jan 7, 2020) 		paternalclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedpaternalyes1not providednot provided1not providedclinical testing

Citations

PubMed

Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia.

Shiang R, Ryan SG, Zhu YZ, Hahn AF, O'Connell P, Wasmuth JJ.

Nat Genet. 1993 Dec;5(4):351-8.

PubMed [citation]
PMID:
8298642

Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis.

Elmslie FV, Hutchings SM, Spencer V, Curtis A, Covanis T, Gardiner RM, Rees M.

J Med Genet. 1996 May;33(5):435-6.

PubMed [citation]
PMID:
8733061
PMCID:
PMC1050620
See all PubMed Citations (4)

Details of each submission

From New York Genome Center - CSER-NYCKidSeq, SCV001432901.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The p.Arg299Gln variant (also known as p.Arg271Gln) identified in this individual has been reported in multiple patients affected with autosomal dominant hyperekplexia/startle syndrome, and co-segregates with autosomal dominant hyperekplexia in several families [PMID: 8298642; PMID: 8733061; PMID: 28138086]. The variant is absent from the gnomAD database indicating it is an extremely rare allele in the general population. The variant affects a highly conserved residue and is predicted deleterious by in silico tools. Functional studies have found that the mutant allele results in reduced glycinergic inhibitory neurotransmission by the glycine receptor-channel complex [PMID: 7518444]. Moreover, a different missense variant affecting the same Arg299 of GLRA1 has also been reported in several affected individuals [PMID: 8298642; PMID: 7881416].Based on the available evidence, the p.Arg299Gln variant in the GLRA1 gene is assessed as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyes1not providednot provided1not providednot providednot provided

Last Updated: Nov 24, 2024