NM_001127644.2(GABRA1):c.995C>T (p.Ala332Val) AND Epileptic encephalopathy, early infantile, 19

Clinical significance:Pathogenic (Last evaluated: Jan 21, 2021)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001283749.2

Allele description [Variation Report for NM_001127644.2(GABRA1):c.995C>T (p.Ala332Val)]

NM_001127644.2(GABRA1):c.995C>T (p.Ala332Val)

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.995C>T (p.Ala332Val)
HGVS:
  • NC_000005.10:g.161895804C>T
  • NG_011548.1:g.53614C>T
  • NM_000806.5:c.995C>T
  • NM_001127643.2:c.995C>T
  • NM_001127644.2:c.995C>TMANE SELECT
  • NM_001127645.2:c.995C>T
  • NM_001127648.2:c.995C>T
  • NP_000797.2:p.Ala332Val
  • NP_001121115.1:p.Ala332Val
  • NP_001121116.1:p.Ala332Val
  • NP_001121117.1:p.Ala332Val
  • NP_001121120.1:p.Ala332Val
  • NC_000005.9:g.161322810C>T
Protein change:
A332V; ALA332VAL
Links:
OMIM: 137160.0008
Molecular consequence:
  • NM_000806.5:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127643.2:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127644.2:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127645.2:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127648.2:c.995C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Epileptic encephalopathy, early infantile, 19 (DEE19)
Synonyms:
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 19
Identifiers:
MONDO: MONDO:0014328; MedGen: C3810400; Orphanet: 33069; OMIM: 615744

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001469095OMIMno assertion criteria providedPathogenic
(Jan 21, 2021)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro.

Steudle F, Rehman S, Bampali K, Simeone X, Rona Z, Hauser E, Schmidt WM, Scholze P, Ernst M.

Sci Rep. 2020 Feb 11;10(1):2379. doi: 10.1038/s41598-020-59323-6.

PubMed [citation]
PMID:
32047208
PMCID:
PMC7012862

Details of each submission

From OMIM, SCV001469095.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 13-year-old boy with developmental and epileptic encephalopathy-19 (DEE19; 615744), Steudle et al. (2020) identified a de novo heterozygous c.995C-T transition (c.995C-T, NM_000806.5) in exon 10 of the GABRA1 gene, resulting in an ala332-to-val (A332V) substitution at a conserved residue in the TM3 domain near the subunit interface of the protein. The mutation, which was found by whole-exome sequencing, was not present in the gnomAD database. In vitro studies in HEK293 cells showed that the mutation led to a normal level of protein expression, receptor assembly, and cellular localization, but resulted in increased receptor affinity for diazepam and an abnormal GABA dose response. The patient had his first seizure at age 2.5 months and was diagnosed with epilepsy with complex focal seizures, severe developmental retardation, and optic atrophy at age 18 months.

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

Last Updated: Sep 29, 2021

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