Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003784478 | SCV004572796 | uncertain significance | Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease | 2023-06-15 | 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. This variant disrupts the p.Arg187 amino acid residue in CARD11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30170123). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 CARD11 protein function. This variant has not been reported in the literature in individuals affected with CARD11-related conditions. This variant is present in population databases (rs776851359, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 187 of the CARD11 protein (p.Arg187Gln). |