Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061246 | SCV001225982 | uncertain significance | Severe combined immunodeficiency due to LCK deficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with threonine at codon 397 of the LCK protein (p.Arg397Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs146452317, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with LCK-related conditions. 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. |