Submissions for variant NM_004975.4(KCNB1):c.934C>T (p.Arg312Cys)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255550	SCV000321795	pathogenic	not provided	2022-02-02	criteria provided, single submitter	clinical testing	Published functional studies demonstrate reduction in channel conductance (Kang et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31618753, 31513310, 31600826, 32954514, 34915430, 31785789)
Invitae	RCV000528443	SCV000655445	pathogenic	Developmental and epileptic encephalopathy, 26	2021-05-19	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 312 of the KCNB1 protein (p.Arg312Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant has been observed de novo in families with KCNB1-related disease (Invitae). In at least one family the variant was inherited from an unaffected parent who was apparently germline mosaic (Invitae). ClinVar contains an entry for this variant (Variation ID: 265207). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000528443	SCV000890019	likely pathogenic	Developmental and epileptic encephalopathy, 26	2018-05-28	criteria provided, single submitter	clinical testing
Laboratoire de Génétique Moléculaire Institut de Recherche Necker Enfants Malades, CHU Paris - Hôpital Necker-Enfants Malades	RCV000782147	SCV000920611	pathogenic	Intellectual disability	2019-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001267282	SCV001445463	likely pathogenic	Inborn genetic diseases	2017-12-07	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000528443	SCV004027683	pathogenic	Developmental and epileptic encephalopathy, 26	2023-07-26	criteria provided, single submitter	clinical testing	Criteria applied: PS2,PM1,PM5,PM2_SUP,PP3
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000528443	SCV004239250	pathogenic	Developmental and epileptic encephalopathy, 26	2024-01-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000255550	SCV002035209	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000255550	SCV002038214	pathogenic	not provided		no assertion criteria provided	clinical testing
Kearney Laboratory, Northwestern University Feinberg School of Medicine	RCV000255550	SCV004024587	not provided	not provided		no assertion provided	in vitro