Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001070576 | SCV001235833 | uncertain significance | Neutropenia, severe congenital, 7, autosomal recessive | 2019-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 618 of the CSF3R protein (p.Thr618Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with hereditary CSF3R-related chronic neutrophilia. This variant has been reported in the literature in individuals affected with chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and acute lymphoblastic leukemia, however the germline nature of the variant was confirmed in only one of these individuals (PMID: 27581359, 25491280, 26875968, 28209919, 24614839, 24854193, 28219221, 27148573, 23604229, 28762112, 25932451). ClinVar contains an entry for this variant (Variation ID: 208339). This variant has been reported to affect CSF3R protein function (PMID: 24403076, 30967555, 24081659). 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. |
Clinical Genetics Karolinska University Hospital, |
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 |