ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3516C>G (p.Asp1172Glu) (rs766196697)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188626 SCV000242249 uncertain significance not provided 2014-07-31 criteria provided, single submitter clinical testing p.Asp1172Glu (GAC>GAG): c.3516 C>G in exon 22 of the POLG gene (NM_002693.2). The D1172E variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (M1163R, S1176L) have been reported in association with encephalopathy and progressive external opthalmoplegia (PEO), supporting the functional importance of this region of the protein. However, the D1172E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758328 SCV000886992 likely benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3516C>G (NP_002684.1:p.Asp1172Glu) [GRCH38: NC_000015.10:g.89317503G>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. BP2:The variant is observed in trans/cis with a dominant variant. 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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