ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.1674C>G (p.Phe558Leu) (rs267608668)

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
Illumina Clinical Services Laboratory,Illumina RCV000034141 SCV000915482 uncertain significance Hypomyelinating leukodystrophy 7 2018-03-23 criteria provided, single submitter clinical testing The POLR3A c.1674C>G (p.Phe558Leu) missense variant has been reported in two studies in which it is found in a compound heterozygous state in two individuals, one individual with early onset tremor-ataxia with central hypomyelination in whom the p.Phe558Leu variant was in trans with an inframe insertion, and one individual with 4H leukodystrophy in whom the p.Phe558Leu variant was in trans with a missense variant (Bernard et al. 2011; Wolf et al. 2014). The p.Phe558Leu variant was absent from 250 control chromosomes and is not found in 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Consortium. The evidence for this variant is limited. The p.Phe558Leu variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for pol III-related leukodystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneReviews RCV000034141 SCV000058076 pathologic Hypomyelinating leukodystrophy 7 2012-08-02 no assertion criteria provided curation Converted during submission to Pathogenic.

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.