Submissions for variant NM_172107.4(KCNQ2):c.841G>T (p.Gly281Trp)

dbSNP: rs794727813

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UCLA Clinical Genomics Center, UCLA	RCV000196180	SCV000255396	pathogenic	Developmental and epileptic encephalopathy, 7	2014-04-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000523137	SCV000618030	pathogenic	not provided	2017-10-03	criteria provided, single submitter	clinical testing	The G281W variant has been reported as a de novo in a patient with early infantile epileptic encephalopathy in the published literature and is reported in an additional patient in ClinVar (Landrum et al., 2015; SCV000255396.2; Pisano et al., 2015). This variant is not observed in large population cohorts (Lek et al., 2016). The G281W variant is a non-conservative amino acid substitution that alters a conserved position predicted to be within the pore forming loop between the S5 and S6 transmembrane segments. A different missense change at this residue (G281E) has been identified as a de novo variant at GeneDx in a patient with seizures, and another missense substitution (G281R) has been published as a de novo variant in association with epileptic encephalopathy (Weckhuysen et al., 2013; Zhu et al., 2013). In silico analysis predicts the G281W variant is probably damaging to the protein structure/function. We interpret G281W as a pathogenic variant.
GeneReviews	RCV000196180	SCV000484585	not provided	Developmental and epileptic encephalopathy, 7		no assertion provided	literature only	EE (epileptic encephalopathy)
Channelopathy-Associated Epilepsy Research Center	RCV003315331	SCV004015088	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only