ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1639G>T (p.Ala547Ser)

dbSNP: rs779353857
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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 RCV000758288 SCV000886942 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1639G>T (NP_002684.1:p.Ala547Ser) [GRCH38: NC_000015.10:g.89326685C>A] 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758288 SCV000958612 uncertain significance Progressive sclerosing poliodystrophy 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 547 of the POLG protein (p.Ala547Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs779353857, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV004792430 SCV005411134 uncertain significance not provided 2023-06-09 criteria provided, single submitter clinical testing BP4, PM2_moderate

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