Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000232115 | SCV000291928 | uncertain significance | not provided | 2014-02-26 | criteria provided, single submitter | clinical testing | To our knowledge, the R92Q missense substitution has neither been published as a mutation, nor reported as a benign polymorphism. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R92Q represents a semi-conservative amino acid substitution as a positively charged Arginine residue is replaced with a neutral Glutamine residue. However, this substitution occurs at a position in the ELANE protein that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure or function. Therefore, based on the currently available information, it is unclear whether the R92Q variant is a pathogenic mutation or a rare benign variant. |
| Invitae | RCV001857780 | SCV002290076 | uncertain significance | Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant | 2023-06-20 | 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 ELANE protein function. ClinVar contains an entry for this variant (Variation ID: 242279). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. This variant is present in population databases (rs755088297, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 92 of the ELANE protein (p.Arg92Gln). |
| Genome Diagnostics Laboratory, |
RCV002262837 | SCV002543411 | uncertain significance | Autoinflammatory syndrome | 2016-12-12 | criteria provided, single submitter | clinical testing |