Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187350 | SCV000240935 | uncertain significance | not provided | 2016-11-25 | criteria provided, single submitter | clinical testing | The N304S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The N304S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The N304S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. The presence of N304S in this unaffected parent does not alter the interpretation of this variant, as some individuals with EFHC1 mutations do not develop seizures or epileptiform EEG discharges due to incomplete penetrance (Suzuki et al., 2005; Medina et al., 2008). |
| Fulgent Genetics, |
RCV000764651 | SCV000895772 | uncertain significance | Absence seizure; Juvenile myoclonic epilepsy | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003765177 | SCV001215967 | uncertain significance | Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 304 of the EFHC1 protein (p.Asn304Ser). This variant is present in population databases (rs142107827, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 205393). 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 EFHC1 protein function with a negative predictive value of 80%. 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. |