Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001385122 | SCV001584872 | pathogenic | Hyperinsulinism-hyperammonemia syndrome | 2018-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 503 of the GLUD1 protein (p.Lys503Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with familial hyperinsulinism-hyperammonemia syndrome (PMID: 10871207). 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: "Benign"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. |