ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2915G>A (p.Arg972Gln)

dbSNP: rs200309005
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727299 SCV000242217 uncertain significance not provided 2023-12-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Eurofins Ntd Llc (ga) RCV000727299 SCV000707389 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758463 SCV000887174 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2915G>A (NP_002684.1:p.Arg972Gln) [GRCH38: NC_000015.10:g.89320832C>T] variant in POLG gene is interpretated to be a Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PM1:This variant is in mutational hot spot or a well-studied functional domain without benign variation. PM2:This variant is absent in key population databases. 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. Based on the evidence criteria codes applied, the variant is suggested to be Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758463 SCV001373199 uncertain significance Progressive sclerosing poliodystrophy 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 972 of the POLG protein (p.Arg972Gln). This variant is present in population databases (rs200309005, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 206540). 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 with a positive predictive value of 95%. 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.
Revvity Omics, Revvity RCV000727299 SCV004236435 uncertain significance not provided 2023-11-09 criteria provided, single submitter clinical testing

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