Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001347705 | SCV001541978 | uncertain significance | Pityriasis rubra pilaris; Psoriasis 2 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 466 of the CARD14 protein (p.Glu466Lys). This variant is present in population databases (rs140734867, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043577). 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 CARD14 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. |
Mayo Clinic Laboratories, |
RCV003481086 | SCV004224447 | uncertain significance | not provided | 2022-12-16 | criteria provided, single submitter | clinical testing | BP4 |
Ambry Genetics | RCV004036528 | SCV004920224 | uncertain significance | Inborn genetic diseases | 2024-03-01 | criteria provided, single submitter | clinical testing | The c.1396G>A (p.E466K) alteration is located in exon 10 (coding exon 9) of the CARD14 gene. This alteration results from a G to A substitution at nucleotide position 1396, causing the glutamic acid (E) at amino acid position 466 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003898331 | SCV004717628 | uncertain significance | CARD14-related disorder | 2024-02-01 | no assertion criteria provided | clinical testing | The CARD14 c.1396G>A variant is predicted to result in the amino acid substitution p.Glu466Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |