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NM_001127644.2(GABRA1):c.335G>A (p.Arg112Gln) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 13, 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:
RCV000705072.18

Allele description [Variation Report for NM_001127644.2(GABRA1):c.335G>A (p.Arg112Gln)]

NM_001127644.2(GABRA1):c.335G>A (p.Arg112Gln)

Gene:
GABRA1:gamma-aminobutyric acid type A receptor subunit alpha1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q34
Genomic location:
Preferred name:
NM_001127644.2(GABRA1):c.335G>A (p.Arg112Gln)
Other names:
p.R112Q:CGG>CAG
HGVS:
  • NC_000005.10:g.161873196G>A
  • NG_011548.1:g.31006G>A
  • NM_000806.5:c.335G>A
  • NM_001127643.2:c.335G>A
  • NM_001127644.2:c.335G>AMANE SELECT
  • NM_001127645.2:c.335G>A
  • NM_001127648.2:c.335G>A
  • NP_000797.2:p.Arg112Gln
  • NP_000797.2:p.Arg112Gln
  • NP_001121115.1:p.Arg112Gln
  • NP_001121116.1:p.Arg112Gln
  • NP_001121117.1:p.Arg112Gln
  • NP_001121120.1:p.Arg112Gln
  • NC_000005.9:g.161300202G>A
  • P14867:p.Arg112Gln
Protein change:
R112Q; ARG112GLN
Links:
UniProtKB: P14867#VAR_071809; OMIM: 137160.0004; dbSNP: rs587777308
NCBI 1000 Genomes Browser:
rs587777308
Molecular consequence:
  • NM_000806.5:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127643.2:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127644.2:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127645.2:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127648.2:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Idiopathic generalized epilepsy
Synonyms:
EIG; Generalised epilepsy
Identifiers:
MONDO: MONDO:0005579; MedGen: C0270850; OMIM: 600669; OMIM: PS600669
Name:
Epilepsy, idiopathic generalized, susceptibility to, 13
Synonyms:
EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 5; Epilepsy, juvenile myoclonic 5
Identifiers:
MONDO: MONDO:0012627; MedGen: C4013473; Orphanet: 307; Orphanet: 64280; OMIM: 611136
Name:
Epilepsy, childhood absence 4 (ECA4)
Synonyms:
EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 4
Identifiers:
MedGen: C1970160; Orphanet: 307

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000834052Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 13, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

GABRA1 and STXBP1: novel genetic causes of Dravet syndrome.

Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O'Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Hodgson BL, Gazina EV, Suls A, Shendure J, Dibbens LM, De Jonghe P, et al.

Neurology. 2014 Apr 8;82(14):1245-53. doi: 10.1212/WNL.0000000000000291. Epub 2014 Mar 12.

PubMed [citation]
PMID:
24623842
PMCID:
PMC4001207

De novo GABRA1 mutations in Ohtahara and West syndromes.

Kodera H, Ohba C, Kato M, Maeda T, Araki K, Tajima D, Matsuo M, Hino-Fukuyo N, Kohashi K, Ishiyama A, Takeshita S, Motoi H, Kitamura T, Kikuchi A, Tsurusaki Y, Nakashima M, Miyake N, Sasaki M, Kure S, Haginoya K, Saitsu H, Matsumoto N.

Epilepsia. 2016 Apr;57(4):566-73. doi: 10.1111/epi.13344. Epub 2016 Feb 25.

PubMed [citation]
PMID:
26918889
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000834052.7

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 112 of the GABRA1 protein (p.Arg112Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a variety of seizure phenotypes including early infantile epilepsy and Dravet syndrome (PMID: 24623842, 26918889, 27521439). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127074). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GABRA1 protein function. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 13, 2024