ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.911T>G (p.Leu304Arg) (rs121918044)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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
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; Cerebellar ataxia infantile with progressive external ophthalmoplegia; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4B, MNGIE type 2018-10-31 criteria provided, single submitter clinical testing
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.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000626287 SCV000746945 pathogenic Progressive sclerosing poliodystrophy 2017-12-18 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000014444 SCV000680343 pathogenic Cerebellar ataxia infantile with progressive external ophthalmoplegia 2017-11-08 criteria provided, single submitter clinical testing
OMIM RCV000014444 SCV000034694 pathogenic Cerebellar ataxia infantile with progressive external ophthalmoplegia 2001-07-01 no assertion criteria provided literature only
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.

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