Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001342715 | SCV001536660 | uncertain significance | Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 | 2022-09-19 | 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 expected to disrupt NLRC4 protein function. ClinVar contains an entry for this variant (Variation ID: 1039274). This variant has not been reported in the literature in individuals affected with NLRC4-related conditions. This variant is present in population databases (rs760757972, gnomAD 0.007%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 542 of the NLRC4 protein (p.Glu542Lys). |
Genome Diagnostics Laboratory, |
RCV002264272 | SCV002542379 | uncertain significance | Autoinflammatory syndrome | 2017-12-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003346497 | SCV004074382 | uncertain significance | Inborn genetic diseases | 2023-07-25 | criteria provided, single submitter | clinical testing | The c.1624G>A (p.E542K) alteration is located in exon 4 (coding exon 3) of the NLRC4 gene. This alteration results from a G to A substitution at nucleotide position 1624, causing the glutamic acid (E) at amino acid position 542 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |