Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001040187 | SCV001203748 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 704 of the LRBA protein (p.Met704Ile). This variant is present in population databases (rs114786941, gnomAD 0.2%). 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: 838605). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LRBA protein function. 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 | RCV002551463 | SCV003687819 | uncertain significance | Inborn genetic diseases | 2021-08-09 | criteria provided, single submitter | clinical testing | The c.2112G>A (p.M704I) alteration is located in exon 17 (coding exon 16) of the LRBA gene. This alteration results from a G to A substitution at nucleotide position 2112, causing the methionine (M) at amino acid position 704 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV003442153 | SCV004170046 | uncertain significance | not provided | 2023-05-12 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Mayo Clinic Laboratories, |
RCV003442153 | SCV004227035 | uncertain significance | not provided | 2022-05-25 | criteria provided, single submitter | clinical testing | BP4 |