Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001236854 | SCV001409592 | uncertain significance | Methylcobalamin deficiency type cblG | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 804 of the MTR protein (p.Ile804Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs147387989, ExAC 0.001%). This missense change has been observed in individuals with cobalamin G deficiency (PMID: 12068375; Invitae). 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 disruptive. 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. |