Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003786974 | SCV004574202 | uncertain significance | Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease | 2023-04-03 | 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 CARD11 protein function. This variant has not been reported in the literature in individuals affected with CARD11-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 666 of the CARD11 protein (p.Val666Met). |
| Ambry Genetics | RCV004605036 | SCV005102715 | uncertain significance | Inborn genetic diseases | 2024-06-05 | criteria provided, single submitter | clinical testing | The c.1996G>A (p.V666M) alteration is located in exon 16 (coding exon 15) of the CARD11 gene. This alteration results from a G to A substitution at nucleotide position 1996, causing the valine (V) at amino acid position 666 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |