Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756287 | SCV000884054 | likely pathogenic | not provided | 2017-05-18 | criteria provided, single submitter | clinical testing | The p.Lys331Thr variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP) , and the Exome Aggregation Consortium (ExAC) browser. De novo variants of KCNQ2 are associated with early infantile epileptic encephalopathy 7 (MIM: 602235). Several variants have been identified near the p.Lys331Thr variant (Milh 2013, Millichap 2016 Soldovieri 2016). Milh et al reported a patient with a de novo p.Arg333Trp variant with bilateral tonic clonic and right clonic that improved with age. Soldovieri et al demonstrates that the p.Arg325Gly variant found in four patients was nonfunctional in an in vitro expression system. In a 23 patient cohort, including a nearby p.Ala337Thr variant Millichap et al. described favorable response in 6/11 patients treated with ezogabine. Based on these observations the p.Lys331Thr variant has been classified as likely pathogenic. |