Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000690096 | SCV000817773 | uncertain significance | Erythrocytosis, familial, 3 | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 190 of the EGLN1 protein (p.Ala190Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with EGLN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 569465). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV004025041 | SCV002653902 | uncertain significance | not specified | 2023-07-19 | criteria provided, single submitter | clinical testing | The c.568_569delGCinsTT variant (also known as p.A190L), located in coding exon 1 of the EGLN1 gene, results from an in-frame deletion of GC and insertion of TT at nucleotide positions 568 to 569. This results in the substitution of the alanine residue for a leucine residue at codon 190, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |