Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004048934 | SCV002609178 | uncertain significance | not specified | 2023-09-11 | criteria provided, single submitter | clinical testing | The p.P378S variant (also known as c.1132C>T), located in coding exon 3 of the EGLN1 gene, results from a C to T substitution at nucleotide position 1132. The proline at codon 378 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV003502620 | SCV004313144 | uncertain significance | Erythrocytosis, familial, 3 | 2023-09-05 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects EGLN1 function (PMID: 32755251). 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. 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 disruptive. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 378 of the EGLN1 protein (p.Pro378Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of erythrocytosis (PMID: 29790589, 32755251). ClinVar contains an entry for this variant (Variation ID: 1728806). |