Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001070576 | SCV001235833 | likely pathogenic | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2023-03-15 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects CSF3R function (PMID: 24081659, 24403076, 30967555). 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 CSF3R protein function. ClinVar contains an entry for this variant (Variation ID: 208339). This variant is a well-known somatic variant that has been reported in the literature in individuals affected with chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and acute lymphoblastic leukemia (PMID: 25491280, 26875968, 28209919, 24614839, 24854193, 28219221, 27148573, 23604229, 28762112, 25932451). Rarely, this variant has also been observed as a germline variant in individuals with chronic neutrophilic leukemia (PMID: 31697825, 27581359). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 618 of the CSF3R protein (p.Thr618Ile). |
Clinical Genetics and Genomics, |
RCV001269671 | SCV001449831 | pathogenic | not provided | 2015-11-12 | criteria provided, single submitter | clinical testing | |
Center for Advanced Molecular Diagnostics, |
RCV000190419 | SCV000239865 | pathogenic | Early T cell progenitor acute lymphoblastic leukemia | no assertion criteria provided | clinical testing | Activating CSF3R mutation found in ETP-ALL and chronic neutrophilic leukemia | |
Database of Curated Mutations |
RCV000426562 | SCV000504633 | likely pathogenic | Chronic myelogenous leukemia, BCR-ABL1 positive | 2014-12-26 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436788 | SCV000504634 | likely pathogenic | Acute myeloid leukemia | 2014-10-02 | no assertion criteria provided | literature only |