ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1850G>A (p.Arg617His)

gnomAD frequency: 0.00005  dbSNP: rs779961986
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725018 SCV000333265 uncertain significance not provided 2018-01-12 criteria provided, single submitter clinical testing
GeneDx RCV000725018 SCV000569945 likely benign not provided 2018-05-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 18546365)
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758555 SCV000887290 benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1850G>A (NP_002684.1:p.Arg617His) [GRCH38: NC_000015.10:g.89325549C>T] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BS1:The minor allele frequency of this allele is high for Mitochondrial DNA depletion syndrome 4A (Alpers type). BS2:Observation of the variant in controls is inconsistent with penetrance of Mitochondrial DNA depletion syndrome 4A (Alpers type). Based on the evidence criteria codes applied, the variant is suggested to be Benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758555 SCV001490491 uncertain significance Progressive sclerosing poliodystrophy 2022-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 617 of the POLG protein (p.Arg617His). This variant is present in population databases (rs779961986, 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: 282075). 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.
Athena Diagnostics RCV000725018 SCV002770714 uncertain significance not provided 2022-05-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002519104 SCV003548714 uncertain significance Inborn genetic diseases 2020-12-19 criteria provided, single submitter clinical testing The c.1850G>A (p.R617H) alteration is located in exon 10 (coding exon 9) of the POLG gene. This alteration results from a G to A substitution at nucleotide position 1850, causing the arginine (R) at amino acid position 617 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000725018 SCV003809220 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing

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