Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001216760 | SCV001388572 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2019-07-27 | criteria provided, single submitter | clinical testing | 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 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 has been observed in individuals affected with clinical features of PIGA-related conditions (PMID: 29310717). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 189 of the PIGA protein (p.Lys189Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |