Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001372950 | SCV001569646 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2020-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with serine at codon 35 of the KCNQ2 protein (p.Thr35Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. 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 conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNQ2 protein function. 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. |
New York Genome Center | RCV002265991 | SCV002548965 | uncertain significance | Seizures, benign familial neonatal, 1; Developmental and epileptic encephalopathy, 7 | 2021-08-20 | criteria provided, single submitter | clinical testing |