ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1001G>A (p.Arg334Lys)

gnomAD frequency: 0.00009  dbSNP: rs776437525
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000474734 SCV000543867 uncertain significance Progressive sclerosing poliodystrophy 2022-10-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 334 of the POLG protein (p.Arg334Lys). This variant is present in population databases (rs776437525, gnomAD 0.03%). 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: 405571). 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. 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.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000474734 SCV000887137 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1001G>A (NP_002684.1:p.Arg334Lys) [GRCH38: NC_000015.10:g.89328965C>T] 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. PM2:This variant is absent in key population databases. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV004732887 SCV005350724 uncertain significance POLG-related disorder 2024-05-08 no assertion criteria provided clinical testing The POLG c.1001G>A variant is predicted to result in the amino acid substitution p.Arg334Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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