ClinVar Miner

Submissions for variant NM_198904.4(GABRG2):c.1000G>A (p.Ala334Thr)

gnomAD frequency: 0.00001  dbSNP: rs398123523
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000518838 SCV000111189 uncertain significance not provided 2013-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000518838 SCV000515993 pathogenic not provided 2024-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30190672, 36403551)
Labcorp Genetics (formerly Invitae), Labcorp RCV000797789 SCV000937368 likely pathogenic Epilepsy, childhood absence 2; Febrile seizures, familial, 8 2024-05-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 334 of the GABRG2 protein (p.Ala334Thr). This variant is present in population databases (rs398123523, gnomAD 0.0009%). This missense change has been observed in individuals with GABRG2-related conditions (PMID: 36403551; Invitae). ClinVar contains an entry for this variant (Variation ID: 93433). 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 GABRG2 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000518838 SCV004099128 uncertain significance not provided 2023-09-13 criteria provided, single submitter clinical testing PM2

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