Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186068 | SCV000239037 | pathogenic | not provided | 2015-07-06 | criteria provided, single submitter | clinical testing | It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a positively charged Lysine residue is replaced by a negatively charged Glutamic Acid residue at a position that is near the ornithine binding site in a region of the ornithine transcarbamylase protein that is well conserved in vertebrates (Sakurai et al., 2007; Yamaguchi et al., 2006). Therefore, we interpret K307E to be a disease-associated mutation. The variant is found in OTC panel(s). |
Labcorp Genetics |
RCV001257236 | SCV001433764 | uncertain significance | Ornithine carbamoyltransferase deficiency | 2018-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 307 of the OTC protein (p.Lys307Glu). 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 not been reported in the literature in individuals with OTC-related disease. ClinVar contains an entry for this variant (Variation ID: 203867). 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 and their clinical significance is uncertain. 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. |
Genome- |
RCV001257236 | SCV002033200 | uncertain significance | Ornithine carbamoyltransferase deficiency | 2021-11-07 | criteria provided, single submitter | clinical testing |