ClinVar Miner

Submissions for variant NM_156039.3(CSF3R):c.686C>A (p.Pro229His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691019 SCV000818758 uncertain significance Neutropenia, severe congenital, 7, autosomal recessive 2018-04-02 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 229 of the CSF3R protein (p.Pro229His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with severe congenital neutropenia (PMID: 10449521). This variant is also known as 850C>A or Pro206His in the literature. Experimental studies using myeloid cells have shown that this missense change acts in a dominant negative fashion to abrogate G-CSF–mediated proliferation and survival signals by reduced ligand binding and reduced STAT activation (PMID: 10449521). 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.

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