Submissions for variant NM_001972.4(ELANE):c.354C>G (p.Ile118Met)

gnomAD frequency: 0.00002  dbSNP: rs759734732

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001796400	SCV001403336	uncertain significance	Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant	2023-09-21	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. 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 ELANE protein function. ClinVar contains an entry for this variant (Variation ID: 957791). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. This variant is present in population databases (rs759734732, gnomAD 0.02%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 118 of the ELANE protein (p.Ile118Met). 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.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989649	SCV004806461	uncertain significance	Neutropenia, severe congenital, 1, autosomal dominant	2024-03-25	criteria provided, single submitter	clinical testing