ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.3235A>C (p.Ile1079Leu)

dbSNP: rs756393846
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758325 SCV000886989 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3235A>C (NP_002684.1:p.Ile1079Leu) [GRCH38: NC_000015.10:g.89318969T>G] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV003326492 SCV004033411 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing POLG: PM2, PS4:Supporting
Labcorp Genetics (formerly Invitae), Labcorp RCV000758325 SCV004297674 uncertain significance Progressive sclerosing poliodystrophy 2023-04-12 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt POLG protein function. ClinVar contains an entry for this variant (Variation ID: 619337). This missense change has been observed in individual(s) with autosomal dominant progressive external ophthalmoplegia (PMID: 18546365). This variant is present in population databases (rs756393846, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1079 of the POLG protein (p.Ile1079Leu).

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