ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3216C>G (p.Thr1072=) (rs146936870)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186651 SCV000171111 benign not specified 2013-10-18 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723849 SCV000203325 uncertain significance not provided 2017-11-01 criteria provided, single submitter clinical testing
Invitae RCV000697212 SCV000825809 uncertain significance Progressive sclerosing poliodystrophy 2019-11-18 criteria provided, single submitter clinical testing This sequence change affects codon 1072 of the POLG mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POLG protein. This variant is present in population databases (rs146936870, ExAC 0.02%). This variant has not been reported in the literature in individuals with POLG-related disease. ClinVar contains an entry for this variant (Variation ID: 138757). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000697212 SCV000887277 likely benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3216C>G (NP_002684.1:p.Thr1072=) [GRCH38: NC_000015.10:g.89318988G>C] 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. BS1:The minor allele frequency of this allele is high for Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723849 SCV001149557 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing

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