ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.1930G>A (p.Glu644Lys) (rs755165065)

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
GeneDx RCV000414392 SCV000491316 likely pathogenic not provided 2016-06-08 criteria provided, single submitter clinical testing The E644K variant in the POLR3A gene has been reported previously in three unrelated patients with hypomyelinating leukodystrophy who were heterozygous for the E644K variant and heterozygous for another variant (Wolf et al., 2014). The E644K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E644K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The E644K variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
GeneReviews RCV001541990 SCV001760627 pathogenic Hypomyelinating leukodystrophy 7 2017-05-11 no assertion criteria provided literature only

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.