Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000706754 | SCV000835823 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2018-06-07 | criteria provided, single submitter | clinical testing | A different missense substitution at this codon (p.His127Asp) has been reported to be de novo in individuals affected with Dravet syndrome (PMID: 21248271). This variant identified in the SCN1A gene is located in the transmembrane spanning D1-S1 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. For these reasons, this variant has been classified as Likely Pathogenic. 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: "Benign"; Align-GVGD: "Class C65"). This variant has been observed to be de novo in an individual affected with early infantile epileptic encephalopathy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 127 of the SCN1A protein (p.His127Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Mendelics | RCV002249425 | SCV002519044 | pathogenic | Generalized epilepsy with febrile seizures plus, type 2 | 2022-05-04 | criteria provided, single submitter | clinical testing |