Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Geisinger Autism and Developmental Medicine Institute, |
RCV000678327 | SCV000804389 | uncertain significance | Developmental and epileptic encephalopathy, 11 | 2018-03-09 | criteria provided, single submitter | provider interpretation | This variant was identified in a 9 year old female with intellectual disability, multiple congenital anomalies, and dysmorphic facial features. It was inherited from a healthy father who had febrile seizures as a child, as did his brother who has not been tested. This variant is absent from the gnomAD database and computational prediction models are inconsistent. This variant has not been reported previously in the literature, to our knowledge. Clinical correlation with SCN2A-related disorders was thought to be poor. Additionally, whole exome sequencing also identified an additional variant of uncertain significance. |
Invitae | RCV002517895 | SCV003490754 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-08-17 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 207036). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 74 of the SCN2A protein (p.Val74Met). |