ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2654C>G (p.Thr885Ser)

dbSNP: rs1224799376
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798129 SCV000937728 uncertain significance Progressive sclerosing poliodystrophy 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 885 of the POLG protein (p.Thr885Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the same chromosome (in cis) with a pathogenic variant (p.Ala467Thr) in POLG in an individual affected with clinical features of Alpers syndrome (PMID: 16621917). Experimental studies have shown that this change results in slight to moderate reduction in DNA-binding affinity, but does not affect the overall stability or enzymatic activity of the POLG protein (PMID: 19478085). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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.