ClinVar Miner

Submissions for variant NM_000814.6(GABRB3):c.863C>T (p.Thr288Ile)

dbSNP: rs1555401440
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624329 SCV000742781 likely pathogenic Inborn genetic diseases 2017-08-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767831 SCV004589170 pathogenic Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 288 of the GABRB3 protein (p.Thr288Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 34698933). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 521964). 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 GABRB3 protein function with a positive predictive value of 95%. This variant disrupts the p.Thr288 amino acid residue in GABRB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29162865). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.