ClinVar Miner

Submissions for variant NM_001127644.2(GABRA1):c.85C>T (p.Pro29Ser) (rs143815396)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724850 SCV000230134 uncertain significance not provided 2015-05-27 criteria provided, single submitter clinical testing
GeneDx RCV000187511 SCV000241105 uncertain significance not specified 2017-06-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GABRA1 gene. The P29S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P29S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. The P29S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000645390 SCV000767135 uncertain significance Idiopathic generalized epilepsy; Epilepsy, juvenile myoclonic 5; Epilepsy, childhood absence 4 2019-07-15 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 29 of the GABRA1 protein (p.Pro29Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs143815396, ExAC 0.05%). This variant has not been reported in the literature in individuals with GABRA1-related disease. ClinVar contains an entry for this variant (Variation ID: 197167). Experimental studies have shown that this missense change is associated with a reduction in channel current density (PMID: 27622563). 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.

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