Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000534369 | SCV000644903 | uncertain significance | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 | 2017-02-04 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs765672206, ExAC 0.006%) but has not been reported in the literature in individuals with a PIK3R2-related disease. This sequence change replaces glutamic acid with lysine at codon 515 of the PIK3R2 protein (p.Glu515Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. |