ClinVar Miner

Submissions for variant NM_022051.3(EGLN1):c.493C>G (p.Pro165Ala)

dbSNP: rs200502960
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001324086 SCV001515025 uncertain significance Erythrocytosis, familial, 3 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 165 of the EGLN1 protein (p.Pro165Ala). 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 variant has not been reported in the literature in individuals affected with EGLN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023965). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001324086 SCV004047421 uncertain significance Erythrocytosis, familial, 3 criteria provided, single submitter clinical testing The missense variant c.493C>G (p.Pro165Ala) in EGLN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Pro165Ala variant has allele frequency of 0.0023% in the gnomad and novel in 1000 genome database. This variant has been reported to the ClinVar database as Uncertain significance (VUS). The amino acid Pro at position 165 is changed to a Ala changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Pro165Ala in EGLN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.