Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000636297 | SCV000757736 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2017-09-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with KCNQ2-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant is present in population databases (rs747050726, ExAC 0.003%). This sequence change replaces isoleucine with valine at codon 238 of the KCNQ2 protein (p.Ile238Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |
Channelopathy- |
RCV003315358 | SCV004015075 | not provided | Complex neurodevelopmental disorder | no assertion provided | literature only |