Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002045336 | SCV002293022 | uncertain significance | Transcobalamin II deficiency | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 252 of the TCN2 protein (p.Phe252Leu). This variant is present in population databases (rs142553702, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1503071). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |