Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187529 | SCV000241123 | pathogenic | not provided | 2012-09-06 | criteria provided, single submitter | clinical testing | p.Leu307Val (TTA>GTA):c.919 T>G in exon 7 of the GABRG2 gene (NM_000816.3) The Leu307Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Leu307Val in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Leu307Val alters a highly conserved position in the second transmembrane domain of the GABRG2 protein. The amino acid substitution is conservative, as both Leucine and Valine are uncharged, non-polar amino acids of similar size. While some in silico algorithms predict that Leu307Val is damaging to protein structure/function, other models predict that it is benign. Therefore, the currently available information suggests that L307V is pathogenic. This variant has been observed de novo without verified parentage. The variant is found in EPILEPSY panel(s). |
| Invitae | RCV001857614 | SCV002286356 | uncertain significance | Epilepsy, childhood absence 2; Febrile seizures, familial, 8 | 2021-09-15 | criteria provided, single submitter | clinical testing | 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. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 205548). This missense change has been observed in individual(s) with clinical features of GABRG2-related conditions (PMID: 29655203, 30557390). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 307 of the GABRG2 protein (p.Leu307Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |