Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686265 | SCV000813776 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1088 of the LRBA protein (p.Glu1088Gln). This variant is present in population databases (rs142075710, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 566454). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRBA protein function with a negative predictive value of 80%. 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. |
ARUP Laboratories, |
RCV000756317 | SCV000884087 | uncertain significance | not provided | 2018-01-09 | criteria provided, single submitter | clinical testing | The p.Glu1088Gln variant (rs142075710) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.04 percent (identified on 50 out of 276,512 chromosomes). The glutamic acid at position 1088 is weakly conserved considering 13 species (Alamut v2.10) and computational analyses of the effects of the p.Glu1088Gln variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Glu1088Gln variant with certainty. |
Ambry Genetics | RCV002547096 | SCV003689078 | uncertain significance | Inborn genetic diseases | 2022-11-10 | criteria provided, single submitter | clinical testing | The c.3262G>C (p.E1088Q) alteration is located in exon 23 (coding exon 22) of the LRBA gene. This alteration results from a G to C substitution at nucleotide position 3262, causing the glutamic acid (E) at amino acid position 1088 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |