Submissions for variant NM_000814.6(GABRB3):c.551A>G (p.Tyr184Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003808591	SCV004590974	pathogenic	Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5	2023-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 184 of the GABRB3 protein (p.Tyr184Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. 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. For these reasons, this variant has been classified as Pathogenic.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV004527468	SCV005039010	likely pathogenic	Seizure	2024-05-03	criteria provided, single submitter	clinical testing