Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000265782 | SCV000341501 | uncertain significance | not provided | 2016-06-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001379975 | SCV001577891 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with tryptophan at codon 848 of the SCN8A protein (p.Leu848Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of epileptic encephalopathy (PMID: 31026061, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 287663). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |