Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001219622 | SCV001391570 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2019-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 293 of the KCNQ2 protein (p.Leu293Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in cis with a second adjacent missense variant in an individual with epilepsy and/or neurodevelopmental disease (PMID: 29655203). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Channelopathy- |
RCV003315364 | SCV004015098 | not provided | Complex neurodevelopmental disorder | no assertion provided | literature only |