ClinVar Miner

Submissions for variant NM_001126131.2(POLG):c.911T>G (p.Leu304Arg) (rs121918044)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188648 SCV000242271 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing The L304R pathogenic variant in the POLG gene has been previously reported in both the homozygous andcompound heterozygous state in individuals with POLG-related disorders including Alpers syndrome, autosomalrecessive progressive external ophthalmoplegia (arPEO), and ataxic neuropathy (Van Goethem et al., 2001; Tang etal., 2011; Human DNA Polymerase Gamma Mutation Database). Therefore, L304R is considered to be a pathogenicvariant.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000188648 SCV000610658 likely pathogenic not provided 2017-04-21 criteria provided, single submitter clinical testing
Institute of Human Genetics, Klinikum rechts der Isar RCV000014444 SCV000680343 pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 2017-11-08 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000626287 SCV000746945 pathogenic Progressive sclerosing poliodystrophy 2017-12-18 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000626287 SCV000886922 likely pathogenic Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.911T>G (NP_002684.1:p.Leu304Arg) [GRCH38: NC_000015.10:g.89329055A>C] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:11431686 . This variant meets the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. PM3:Detected in trans with a pathogenic variant for Mitochondrial DNA depletion syndrome 4A (Alpers type) which is a recessive disorder. PP1:This variant is co-segregated with Mitochondrial DNA depletion syndrome 4A (Alpers type) in multiple affected family members. PP2:This is a missense variant in POLG with a low rate of benign and high rate of pathogenic missense variations. PP3:Computational evidence/predictors indicate the variant has deleterious effect on POLG structure, function, or protein-protein interaction. PP4:Patient's phenotype or family history is highly specific for POLG. Based on the evidence criteria codes applied, the variant is suggested to be Likely Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762954 SCV000893386 pathogenic Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1 (MNGIE type); Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome; Mitochondrial DNA depletion syndrome 4B, MNGIE type 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000626287 SCV001212784 pathogenic Progressive sclerosing poliodystrophy 2020-03-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 304 of the POLG protein (p.Leu304Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is present in population databases (rs121918044, ExAC 0.04%). This variant has been observed in individuals with autosomal recessive POLG-related disorders (PMID: 21880868, 22006280, 16639411, 11431686, 24288107). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 13497). This variant has been reported to affect POLG protein function (PMID: 20601675, 26095671). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV000014444 SCV001426445 pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 criteria provided, single submitter clinical testing
Ambry Genetics RCV001266602 SCV001444778 pathogenic Inborn genetic diseases 2019-02-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000626287 SCV001524402 pathogenic Progressive sclerosing poliodystrophy 2020-02-06 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
OMIM RCV000014444 SCV000034694 pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 2001-07-01 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.