Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000232534 | SCV000291940 | likely pathogenic | not provided | 2014-09-23 | criteria provided, single submitter | clinical testing | To our knowledge, this variant has neither been published as a mutation, nor reported as a benign polymorphism to our knowledge. R143C represents a non-conservative amino acid substitution, as a large, positively-charged Arginine residue is replaced with a smaller, neutral Cysteine residue, which could alter the normal disulfide bonds in the protein. The position in the ELANE protein where this substitution occurs is not highly conserved among species; however, the R143C substitution 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. Therefore, R143C is a strong candidate for a disease-causing mutation; however, the possibility that it is a benign variant cannot be excluded. |
Invitae | RCV001857782 | SCV002310588 | uncertain significance | Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant | 2023-09-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 242291). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 143 of the ELANE protein (p.Arg143Cys). This variant is present in population databases (rs199558534, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of ELANE-related neutropenia (PMID: 35047849). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ELANE protein function. 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. |
Genome Diagnostics Laboratory, |
RCV002262841 | SCV002543417 | uncertain significance | Autoinflammatory syndrome | 2016-12-12 | criteria provided, single submitter | clinical testing |