Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004262011 | SCV003889997 | uncertain significance | not specified | 2023-01-24 | criteria provided, single submitter | clinical testing | The c.117C>G (p.C39W) alteration is located in exon 1 (coding exon 1) of the IRF7 gene. This alteration results from a C to G substitution at nucleotide position 117, causing the cysteine (C) at amino acid position 39 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003750952 | SCV004531846 | uncertain significance | Immunodeficiency 39 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 39 of the IRF7 protein (p.Cys39Trp). This variant is present in population databases (rs767751130, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with IRF7-related conditions. ClinVar contains an entry for this variant (Variation ID: 2472428). 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 IRF7 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. |