ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1370G>A (p.Arg457Gln)

gnomAD frequency: 0.00001  dbSNP: rs372911506
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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 RCV000699631 SCV000828351 uncertain significance Progressive sclerosing poliodystrophy 2022-07-12 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 457 of the POLG protein (p.Arg457Gln). This variant is present in population databases (rs372911506, gnomAD 0.01%). This missense change has been observed in individual(s) with asymmetric ataxia, depression, memory loss, epilepsy, and axonal neuropathy (PMID: 29278894). ClinVar contains an entry for this variant (Variation ID: 576988). 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.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000699631 SCV000886935 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1370G>A (NP_002684.1:p.Arg457Gln) [GRCH38: NC_000015.10:g.89327230C>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. PM2:This variant is absent in key population databases. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.
GeneDx RCV003322812 SCV004028105 uncertain significance not provided 2023-08-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29278894, 34194468)

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