ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.2121C>A (p.Asn707Lys) (rs755502359)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430154 SCV000518193 likely benign not specified 2015-07-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758297 SCV000886952 likely benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.2121C>A (NP_002684.1:p.Asn707Lys) [GRCH38: NC_000015.10:g.89323851G>T] variant in POLG gene is interpretated to be a Likely Benign 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. BP6:Reputable source(s) without shared data suggest the variant is benign. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000995415 SCV001149566 uncertain significance not provided 2018-03-01 criteria provided, single submitter clinical testing
Invitae RCV000758297 SCV001419141 uncertain significance Progressive sclerosing poliodystrophy 2019-10-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 707 of the POLG protein (p.Asn707Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs755502359, ExAC 0.01%). This variant has not been reported in the literature in individuals with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 380291). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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