Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688018 | SCV000815614 | uncertain significance | Hyperkalemic periodic paralysis | 2021-10-18 | criteria provided, single submitter | clinical testing | 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 disruptive. This missense change has been observed in individual(s) with clinical features of SCN4A-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 1322 of the SCN4A protein (p.Ala1322Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. |