Submissions for variant NM_000760.4(CSF3R):c.1182C>G (p.Ser394Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002597528	SCV002956743	uncertain significance	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	2022-10-05	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. 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 not expected to disrupt CSF3R protein function. This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. This variant is present in population databases (rs775126057, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 394 of the CSF3R protein (p.Ser394Arg).
PreventionGenetics, part of Exact Sciences	RCV004756407	SCV005363884	uncertain significance	CSF3R-related disorder	2024-06-20	no assertion criteria provided	clinical testing	The CSF3R c.1182C>G variant is predicted to result in the amino acid substitution p.Ser394Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.