ClinVar Miner

Submissions for variant NM_001364905.1(LRBA):c.3262G>C (p.Glu1088Gln)

gnomAD frequency: 0.00023  dbSNP: rs142075710
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Total submissions: 3
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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, Molecular Genetics and Genomics, 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.

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