Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001983408 | SCV002267982 | uncertain significance | Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease | 2022-10-13 | 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) 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. ClinVar contains an entry for this variant (Variation ID: 1489727). This variant has not been reported in the literature in individuals affected with CARD11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 72 of the CARD11 protein (p.Arg72Gln). |
| Gene |
RCV003236919 | SCV003935467 | pathogenic | not provided | 2022-12-20 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate R27Q exhibits a dominant-negative effect impairing at least two steps of the CARD11 signaling cycle (Bedsaul et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35198875, 33864281) |