Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000533201 | SCV000639646 | likely pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2018-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with alanine at codon 229 of the SCN2A protein (p.Ser229Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported to be de novo in an individual affected with seizures (Invitae database). ClinVar contains an entry for this variant (Variation ID: 464920). |