Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000817196 | SCV000957744 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2018-11-28 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LRBA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 1953 of the LRBA protein (p.Leu1953Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. |