ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.331G>C (p.Gly111Arg)

gnomAD frequency: 0.00004  dbSNP: rs760170099
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000995421 SCV001149581 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858812 SCV002193652 uncertain significance Progressive sclerosing poliodystrophy 2023-07-17 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POLG protein function. 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. ClinVar contains an entry for this variant (Variation ID: 807308). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 111 of the POLG protein (p.Gly111Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with POLG-related conditions.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002067611 SCV002495900 uncertain significance Progressive sclerosing poliodystrophy; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b 2021-05-17 criteria provided, single submitter clinical testing POLG NM_002693.2 exon 2 p.Gly111Arg (c.331G>C): This variant has not been reported in the literature but is present in 0.01% (5/41474) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-89333424-C-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:807308). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV002479171 SCV002792178 uncertain significance Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b 2021-07-11 criteria provided, single submitter clinical testing

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.