Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522032 | SCV000621281 | likely benign | not provided | 2019-03-26 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 29635106) |
Ce |
RCV000522032 | SCV001152478 | uncertain significance | not provided | 2016-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001214677 | SCV001386371 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 467 of the SCN2A protein (p.Ala467Thr). This variant is present in population databases (rs745774658, gnomAD 0.02%). This missense change has been observed in individuals with clinical features of SCN2A-related conditions (PMID: 29635106; Invitae). In some individuals, the variant was inherited from an unaffected parent. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 452471). 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 SCN2A protein function with a negative predictive value of 95%. 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 | RCV001542304 | SCV001760989 | uncertain significance | Developmental and epileptic encephalopathy, 11 | 2020-07-10 | criteria provided, single submitter | clinical testing | The inherited c.1399G>A (p.Ala467Thr) variant identified in the SCN2A gene substitutes a moderately conserved Alanine for Threonine at amino acid 467/2006 (exon 11/27). Threonine is present at this position in several smaller vertebrates including some species of bird and bat. This variant is found with low frequency in gnomAD(v3.0) (5 heterozygotes, 0 homozygotes; allele frequency: 3.49e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Deleterious (Provean; score:-0.42) and Damaging (SIFT; score:0.363) to the function of the canonical transcript. The c.1399G>A (p.Ala467Thr) variant is reported in ClinVar as a Variant of Uncertain Significance (VarID:452471), and has been reported in one family with SCN2A-associated seizure disorder [PMID:29635106]. The p.Ala467 residue is not within a mapped domain of SCN2A (UniProtKB:Q99250). Given the lack of compelling evidence for its pathogenicity, the inherited c.1399G>A (p.Ala467Thr) variant identified in the SCN2A gene is reported as a Variant of Uncertain Significance. |
Revvity Omics, |
RCV000522032 | SCV003820757 | uncertain significance | not provided | 2019-12-09 | criteria provided, single submitter | clinical testing |