ClinVar Miner

Submissions for variant NM_001972.4(ELANE):c.581_582inv (p.Gln194Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483486 SCV000571193 uncertain significance not provided 2017-03-30 criteria provided, single submitter clinical testing To our knowledge, the c.581_582delAGinsCT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant. The variant is observed in 6/16428 (0.037%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). The c.581_582delAGinsCT variant results in an in-frame substitution of one amino acid, denoted p.Q194P. It occurs at a position within the peptidase S1 domain that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. However, missense variants in nearby residues (R191S, R193Q) have been reported in the Human Gene Mutation Database in association with congenital neutropenia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV002526614 SCV003519148 uncertain significance Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant 2022-09-09 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 421871). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.4%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 194 of the ELANE protein (p.Gln194Pro).

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