ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.855G>C (p.Gln285His)

gnomAD frequency: 0.00001  dbSNP: rs141367015
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188644 SCV000242267 uncertain significance not provided 2024-02-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Eurofins Ntd Llc (ga) RCV000188644 SCV000859312 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758410 SCV000887104 uncertain significance Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.855G>C (NP_002684.1:p.Gln285His) [GRCH38: NC_000015.10:g.89330081C>G] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. 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 Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758410 SCV001558371 uncertain significance Progressive sclerosing poliodystrophy 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 285 of the POLG protein (p.Gln285His). This variant also falls at the last nucleotide of exon 3, which is part of the consensus splice site for this exon. This variant is present in population databases (rs141367015, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 206584). 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 RCV000188644 SCV002541298 uncertain significance not provided 2021-10-21 criteria provided, single submitter clinical testing

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