Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000997254 | SCV001152475 | uncertain significance | not provided | 2019-05-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002454245 | SCV002615161 | uncertain significance | Inborn genetic diseases | 2018-01-19 | criteria provided, single submitter | clinical testing | The p.I123V variant (also known as c.367A>G), located in coding exon 2 of the SCN2A gene, results from an A to G substitution at nucleotide position 367. The isoleucine at codon 123 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002550708 | SCV002989752 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2022-08-20 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 808842). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 123 of the SCN2A protein (p.Ile123Val). |