Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000705694 | SCV000834705 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2018-03-17 | criteria provided, single submitter | clinical testing | This variant has been reported in an individual affected with a mitochondrial abnormality (PMID: 26633542). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 365 of the SCN1A protein (p.Phe365Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant identified in the SCN1A gene is located in the extracellular D1-P1 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. |