Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000416050 | SCV000493560 | uncertain significance | not provided | 2016-07-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000540777 | SCV000646967 | pathogenic | Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 | 2020-03-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed to be de novo in individuals affected with early-onset absence epilepsy (PMID: 28053010, Invitae). ClinVar contains an entry for this variant (Variation ID: 374687). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 127 of the GABRB3 protein (p.Lys127Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. |
Gene |
RCV000416050 | SCV001825330 | pathogenic | not provided | 2022-09-28 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect by significantly reducing GABA sensitivity and channel current amplitude (Absalom et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28053010, 32964447, 34906499, 31785789, 35383156) |