ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.2596C>T (p.Arg866Trp)

gnomAD frequency: 0.00003  dbSNP: rs748777396
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000591696 SCV000709289 uncertain significance not provided 2017-06-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000690248 SCV000817929 uncertain significance Progressive sclerosing poliodystrophy 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 866 of the POLG protein (p.Arg866Trp). This variant is present in population databases (rs748777396, gnomAD 0.007%). This missense change has been observed in individual(s) with Parkinson’s disease (PMID: 32613234). ClinVar contains an entry for this variant (Variation ID: 502515). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000591696 SCV001715129 uncertain significance not provided 2020-01-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002438544 SCV002745437 uncertain significance Inborn genetic diseases 2018-04-23 criteria provided, single submitter clinical testing The p.R866W variant (also known as c.2596C>T), located in coding exon 15 of the POLG gene, results from a C to T substitution at nucleotide position 2596. The arginine at codon 866 is replaced by tryptophan, an amino acid with dissimilar properties. In one study, this alteration was detected in 2/796 Japanese individuals with bipolar disorder and in 1/767 controls (Kasahara T et al. Psychiatry Clin. Neurosci., 2017 Aug;71:518-529). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Athena Diagnostics RCV000591696 SCV004229887 uncertain significance not provided 2023-05-19 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging.

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