Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001855321 | SCV002168618 | uncertain significance | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 815 of the SCN3A protein (p.Asp815Asn). This variant is present in population databases (rs755440336, gnomAD 0.02%). This missense change has been observed in individual(s) with early-onset focal epilepsy (PMID: 24157694). This variant is also known as D766N. ClinVar contains an entry for this variant (Variation ID: 522564). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN3A protein function. Experimental studies have shown that this missense change affects SCN3A function (PMID: 24157691). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252180 | SCV002523930 | uncertain significance | See cases | 2021-02-22 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4, PM2, PP3 |
| OMIM | RCV000625709 | SCV000746209 | pathogenic | Epilepsy, familial focal, with variable foci 4 | 2020-09-01 | no assertion criteria provided | literature only |