ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3505G>A (p.Gly1169Ser) (rs753864625)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188625 SCV000242248 uncertain significance not provided 2016-01-27 criteria provided, single submitter clinical testing The G1169S 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. The G1169S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across most mammalian species, and multiple missense mutations in nearby residues have been reported in the Human DNA Polymerase Gamma Mutation Database in association with POLG-related disorders, supporting the functional importance of this region of the protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Fulgent Genetics,Fulgent Genetics RCV000765234 SCV000896470 uncertain significance Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1 (MNGIE type); Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1; Cerebellar ataxia infantile with progressive external ophthalmoplegia; Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome; Mitochondrial DNA depletion syndrome 4B, MNGIE type 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000188625 SCV001149554 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing

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