Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002957313 | SCV003269998 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1003 of the SCN1A protein (p.Thr1003Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2059846). 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 SCN1A protein function. 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 | RCV004958859 | SCV005499996 | uncertain significance | Inborn genetic diseases | 2024-12-07 | criteria provided, single submitter | clinical testing | The c.3008C>T (p.T1003I) alteration is located in exon 16 (coding exon 16) of the SCN1A gene. This alteration results from a C to T substitution at nucleotide position 3008, causing the threonine (T) at amino acid position 1003 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |