Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000226068 | SCV000291932 | uncertain significance | not specified | 2012-11-21 | criteria provided, single submitter | clinical testing | G148R represents a non-conservative amino acid substitution, as a small, non-polar Glycine residue is replaced with a large, positively-charged Arginine residue. The position in the ELANE protein where this substitution occurs is not highly conserved among species; however, a mutation in a neighboring codon (C151S, reported as C122S) has been observed in association with ELANE-related neutropenia (Ancliff et al., 2001). Therefore, based on the currently available information, it is unclear whether G148R is a disease-causing mutation or a rare benign variant. |
Genome Diagnostics Laboratory, |
RCV002262838 | SCV002543419 | uncertain significance | Autoinflammatory syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002518392 | SCV003512889 | uncertain significance | Cyclical neutropenia; Neutropenia, severe congenital, 1, autosomal dominant | 2023-06-06 | 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 242283). This variant has not been reported in the literature in individuals affected with ELANE-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 148 of the ELANE protein (p.Gly148Arg). |