Submissions for variant NM_000814.6(GABRB3):c.437A>C (p.Asp146Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003009959	SCV003304694	uncertain significance	Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5	2022-06-04	criteria provided, single submitter	clinical testing	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. 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. This variant has not been reported in the literature in individuals affected with GABRB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 146 of the GABRB3 protein (p.Asp146Ala).
Institute of Human Genetics, University of Leipzig Medical Center	RCV003128319	SCV003804653	uncertain significance	Developmental and epileptic encephalopathy, 43	2023-02-03	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PM2_SUP, PP3