Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000809742 | SCV000949915 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2023-07-21 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 653893). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 732 of the LRBA protein (p.Ser732Asn). |
| Neuberg Centre For Genomic Medicine, |
RCV000809742 | SCV004176435 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2023-03-01 | criteria provided, single submitter | clinical testing | The missense variant c.2195G>A (p.Ser732Asn) in the LRBA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0004%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Serine at position 732 is changed to a Asparagine changing protein sequence and it might alter its composition and physico- chemical properties. The amino acid change p.Ser732Asn in LRBA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |
| Center for Genomic Medicine, |
RCV000809742 | SCV005373900 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2024-09-22 | criteria provided, single submitter | clinical testing |