Submissions for variant NM_004975.4(KCNB1):c.1202G>C (p.Gly401Ala)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003019502	SCV003321823	likely pathogenic	Developmental and epileptic encephalopathy, 26	2022-02-23	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly401 amino acid residue in KCNB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26477325, 31513310). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 KCNB1 protein function. This missense change has been observed in individual(s) with clinical features of KCNB1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 401 of the KCNB1 protein (p.Gly401Ala).