Submissions for variant NM_004975.4(KCNB1):c.1121C>T (p.Thr374Ile)

dbSNP: rs587777849

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000444433	SCV000515939	pathogenic	not provided	2018-11-12	criteria provided, single submitter	clinical testing	The T374I variant in the KCNB1 gene has been reported previously de novo in anindividual with epileptic encephalopathy and infantile spasms. Functional studies indicated that this substitution affects ion selectivity and causes channel dysfunction (Torkamani et al., 2014). The T374I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T374I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position in Segment H5 of the Pore-forming Intramembrane domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T374I as a pathogenic variant.
Molecular Genetics Lab, CHRU Brest	RCV000144690	SCV004697800	pathogenic	Developmental and epileptic encephalopathy, 26		criteria provided, single submitter	clinical testing
OMIM	RCV000144690	SCV000190029	pathogenic	Developmental and epileptic encephalopathy, 26	2014-10-01	no assertion criteria provided	literature only
Kearney Laboratory, Northwestern University Feinberg School of Medicine	RCV000444433	SCV004024580	not provided	not provided		no assertion provided	in vitro