NM_001127644.2(GABRA1):c.884C>T (p.Thr295Ile) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 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:: RCV001857613.3

Allele description

NM_001127644.2(GABRA1):c.884C>T (p.Thr295Ile)

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.884C>T (p.Thr295Ile)

Other names:

p.T295I:ACA>ATA

HGVS:

NC_000005.10:g.161895693C>T
NG_011548.1:g.53503C>T
NM_000806.5:c.884C>T
NM_001127643.2:c.884C>T
NM_001127644.2:c.884C>TMANE SELECT
NM_001127645.2:c.884C>T
NM_001127648.2:c.884C>T
NP_000797.2:p.Thr295Ile
NP_001121115.1:p.Thr295Ile
NP_001121116.1:p.Thr295Ile
NP_001121117.1:p.Thr295Ile
NP_001121120.1:p.Thr295Ile
NC_000005.9:g.161322699C>T

Protein change:

T295I

Links:

dbSNP: rs796052496

NCBI 1000 Genomes Browser:

rs796052496

Molecular consequence:

NM_000806.5:c.884C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127643.2:c.884C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127644.2:c.884C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127645.2:c.884C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127648.2:c.884C>T - 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

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
SCV002216801	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29655203, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002216801

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 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

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

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 Invitae, SCV002216801.3

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 295 of the GABRA1 protein (p.Thr295Ile). 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 GABRA1 protein function. ClinVar contains an entry for this variant (Variation ID: 205525). This missense change has been observed in individual(s) with GABRA1-related conditions (PMID: 29655203). This variant is not present in population databases (gnomAD no frequency).

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine