ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.408C>G (p.Asp136Glu) (rs115109291)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514076 SCV000610955 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000514076 SCV000340284 uncertain significance not provided 2018-08-29 criteria provided, single submitter clinical testing
GeneDx RCV000514076 SCV000242256 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing The D136E missense substitution in the POLG gene was previously identified in two siblings with epilepsy and was considered by the authors to be a variant of unknown clinical significance (Blok et al., 2009). The D136E variant is observed in 0.5-0.6% of alleles from individuals of African background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015). The D136E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicine RCV000758561 SCV000887305 likely benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.408C>G (NP_002684.1:p.Asp136Glu) [GRCH38: NC_000015.10:g.89333347G>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. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.

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