Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001970925 | SCV002258409 | uncertain significance | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 190 of the CSF3R protein (p.Arg190Cys). This variant is present in population databases (rs757569036, gnomAD 0.004%). This missense change has been observed in individual(s) with severe congenital neutropenia (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1473897). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CSF3R protein function with a positive predictive value of 80%. This variant disrupts the p.Arg190 amino acid residue in CSF3R. Other variant(s) that disrupt this residue have been observed in individuals with CSF3R-related conditions (PMID: 30028820), which suggests that this may be a clinically significant amino acid residue. 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. |