Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814123 | SCV000954523 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2018-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 737 of the KCNQ2 protein (p.Gly737Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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. 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. |
| Ambry Genetics | RCV002424916 | SCV002730812 | uncertain significance | Inborn genetic diseases | 2018-04-26 | criteria provided, single submitter | clinical testing | The p.G737D variant (also known as c.2210G>A), located in coding exon 17 of the KCNQ2 gene, results from a G to A substitution at nucleotide position 2210. The glycine at codon 737 is replaced by aspartic acid, an amino acid with similar properties. This variant did not co-segregate with disease in one individual tested in our laboratory. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |