Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000188833 | SCV000242463 | uncertain significance | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | Reported previously as a variant of uncertain significance in an individual with seizures and speech delay; parental segregation studies not performed (Haviland et al., 2022); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the transmembrane segment S1 of the first homologous domain; This variant is associated with the following publications: (PMID: 36403551) |
| Labcorp Genetics |
RCV001221878 | SCV001393947 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-05-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 140 of the SCN1A protein (p.Thr140Ala). This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 206738). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. |