ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.3701G>A (p.Arg1234Gln)

gnomAD frequency: 0.00006  dbSNP: rs750792237
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001731423 SCV000242158 uncertain significance not provided 2021-10-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001852487 SCV002285549 uncertain significance Progressive sclerosing poliodystrophy 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1234 of the POLG protein (p.Arg1234Gln). This variant is present in population databases (rs750792237, gnomAD 0.02%). 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: 206490). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLG protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002485274 SCV002777789 uncertain significance Fanconi anemia complementation group I 2022-04-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001731423 SCV004229896 uncertain significance not provided 2023-09-19 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 not damaging.

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