Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002004674 | SCV002233380 | uncertain significance | Hyperinsulinism-hyperammonemia syndrome | 2021-08-05 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant is also known as C1492A (Phe440Leu). This missense change has been observed in individual(s) with hyperinsulinism-hyperammonemia syndrome (PMID: 10871207). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 493 of the GLUD1 protein (p.Phe493Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. |