ClinVar Miner

Submissions for variant NM_001127644.2(GABRA1):c.869_888del (p.Val290fs)

dbSNP: rs1561587715
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000688675 SCV000816297 pathogenic Idiopathic generalized epilepsy; Epilepsy, idiopathic generalized, susceptibility to, 13; Epilepsy, childhood absence 4 2018-05-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GABRA1 are known to be pathogenic (PMID: 16718694). This variant has not been reported in the literature in individuals with GABRA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val290Glufs*10) in the GABRA1 gene. It is expected to result in an absent or disrupted protein product.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003225952 SCV003922221 likely pathogenic Developmental and epileptic encephalopathy, 19 2023-05-02 criteria provided, single submitter curation The heterozygous p.Val290GlufsTer10 variant in GABRA1 was identified in 1 individual with global development delay without seizures by the Broad Institute Rare Genomes Project. Trio genome analysis showed this variant to be de novo. This variant has not been previously reported in individuals with epileptic encephalopathy, early infantile,19 and was absent from large population studies. This variant has also been reported in ClinVar (Variation ID# 568345) and has been interpreted as pathogenic by Invitae. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 290 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the GABRA1 gene is strongly associated to epileptic encephalopathy, early infantile, 19. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant epileptic encephalopathy, early infantile,19. ACMG/AMP Criteria applied: PVS1_strong, PM2, PS2_moderate (Richards 2015).

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