Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688213 | SCV000815815 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2295 of the LRBA protein (p.Gln2295His). This variant is present in population databases (rs140538555, gnomAD 0.02%). 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: 567991). 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. |
| Ambry Genetics | RCV002544805 | SCV003707229 | uncertain significance | Inborn genetic diseases | 2021-08-12 | criteria provided, single submitter | clinical testing | The c.6885A>C (p.Q2295H) alteration is located in exon 46 (coding exon 45) of the LRBA gene. This alteration results from a A to C substitution at nucleotide position 6885, causing the glutamine (Q) at amino acid position 2295 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |