ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1636C>T (p.Arg546Cys)

gnomAD frequency: 0.00542  dbSNP: rs2307447
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen RCV000020472 SCV001994836 benign Mitochondrial disease 2021-05-07 reviewed by expert panel curation The c.1637C>T (p.Arg546Cys) variant in POLG has been reported with an allele frequency in the African American population at 1.88% in gnomAD. (BA1). In summary, this variant meets criteria to be classified as benign for primary mitochondrial disease inherited in a recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: BA1.
GeneDx RCV001711075 SCV000171139 benign not provided 2019-07-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000127562 SCV000309131 benign not specified criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000473794 SCV000556221 benign Progressive sclerosing poliodystrophy 2024-01-30 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000127562 SCV000803570 benign not specified 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >1% in African population in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.
Athena Diagnostics RCV000127562 SCV000843316 likely benign not specified 2020-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002311516 SCV000846487 benign Inborn genetic diseases 2017-06-22 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000473794 SCV000887273 benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1636C>T (NP_002684.1:p.Arg546Cys) [GRCH38: NC_000015.10:g.89326688G>A] variant in POLG gene is interpretated to be a Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID:19629138 . 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). 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 Benign.
Breakthrough Genomics, Breakthrough Genomics RCV001711075 SCV005294889 benign not provided criteria provided, single submitter not provided

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