Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760614 | SCV000890506 | likely pathogenic | not provided | 2023-12-18 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect through slowing receptor deactivation, decreasing whole cell current compared to wild-type, and absent surface level expression of gamma2 subunit (PMID: 36979350); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36979350) |
Labcorp Genetics |
RCV001855929 | SCV002180998 | pathogenic | Epilepsy, childhood absence 2; Febrile seizures, familial, 8 | 2023-04-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 620250). This variant has not been reported in the literature in individuals affected with GABRG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg224*) in the GABRG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GABRG2 are known to be pathogenic (PMID: 22539854, 22750526, 24407264). |
Ambry Genetics | RCV002360872 | SCV002666739 | pathogenic | Inborn genetic diseases | 2024-11-14 | criteria provided, single submitter | clinical testing | The c.670C>T (p.R224*) alteration, located in exon 6 (coding exon 6) of the GABRG2 gene, consists of a C to T substitution at nucleotide position 670. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 224. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported in an individual with features consistent with GABRG2-related seizure disorders (Hernandez, 2023). Functional analysis demonstrated that the p.R224* variant altered GABAA receptor kinetics, function, and composition (Hernandez, 2023). Based on the available evidence, this alteration is classified as pathogenic. |
Institute of Human Genetics Munich, |
RCV002468604 | SCV002764717 | likely pathogenic | Febrile seizures, familial, 8 | 2021-09-06 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV002468604 | SCV004027745 | pathogenic | Febrile seizures, familial, 8 | 2023-07-04 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1,PS4_MOD,PM2_SUP |