Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702343 | SCV000831195 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2021-02-03 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LRBA-related disease. This variant is present in population databases (rs771839194, ExAC 0.008%). This sequence change replaces cysteine with phenylalanine at codon 94 of the LRBA protein (p.Cys94Phe). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and phenylalanine. |
Gene |
RCV001766541 | SCV001998193 | uncertain significance | not provided | 2019-08-28 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |